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  • Prefrontal cortex is associated with the rapid onset of parental behavior in inexperienced adult mice (C57BL/6)
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-19
    M. Alsina-Llanes; D.E. Olazábal

    There is significant variability in the immediate behavioral response displayed by inexperienced adult mice when exposed to pups for the first time. The aim of this study was to determine which brain regions were engaged (higher c-Fos-immunoreactivity, c-Fos-ir) when virgin females, that were exposed to pups for 15 or 60 min, displayed full parental behavior (FPB), partial parental behavior (PPB), or non-parental behavior (NPB), or virgin males displayed PPB or infanticidal behavior (IB). The number of c-Fos-ir neurons in the prelimbic cortex (PL) was higher in parental females than in the NPB group (after a 15-min exposure), and the group not exposed to pups (NE). C-Fos expression in the nucleus accumbens (NA) was increased in most groups of females exposed to pups compared to NE. Higher c-Fos-ir was also found in the shell subregion of the NA in infanticidal males, compared to males NE. The cortical (CoA) and medial (MA) amygdala also showed higher c-Fos-ir in parental females compared to NE animals. However, PPB and IB male groups also exhibited higher c-Fos-ir in the CoA and MA compared to the NE group. The expression of c-Fos in the different subregions of medial preoptic area and the ventromedial nucleus of the hypothalamus was not specifically associated with either parental or infanticidal behavior. No brain activation in males was specifically associated with infanticidal behavior. Our results suggest that 15 min of exposure to pups is enough to detect brain regions associated with parental behavior (PL) or pups processing (NA, MA, CoA) in mice. The PL might participate in the immediate onset of parental behavior in virgin females, coordinating and planning its rapid execution.

    更新日期:2020-02-20
  • Positive allosteric modulators of alpha 7 nicotinic acetylcholine receptors enhance procognitive effects of conventional anti-Alzheimer drugs in scopolamine-treated rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-19
    Agnieszka Potasiewicz; Martyna Krawczyk; Kinga Gzielo; Piotr Popik; Agnieszka Nikiforuk

    Positive allosteric modulators (PAMs) of alpha 7 nicotinic acetylcholine receptors (α7-nAChRs) may represent a novel approach to attenuate cognitive decline in Alzheimer’s disease (AD). One possible scenario for the use of this class of compounds is their combination with currently approved anti-AD drugs. We thus evaluated the efficacy of co-administration of inactive doses of type I and type II α7-nAChR PAMs (CCMI and PNU-120596, respectively) with acetylcholinesterase inhibitors (AChEIs), donepezil and galantamine, or with a non-competitive glutamate N-methyl-D-aspartate receptor antagonist, memantine, in ameliorating scopolamine-induced memory deficits in the novel object recognition test in rats. Both CCMI and PNU-120596 as well as donepezil, galantamine and memantine attenuated the scopolamine-induced recognition impairments. Interestingly, the combined administration of previously established sub-effective doses of the tested PAMs (0.1 mg/kg) with either AChEIs, donepezil (0.3 mg/kg) and galantamine (0.1 mg/kg), or memantine (0.3 mg/kg) also restored object recognition memory in scopolamine-treated animals. These findings suggest the therapeutic potential of α7-nAChR PAMs as an augmentation strategy for cognitive enhancement in AD.

    更新日期:2020-02-20
  • Towards a Comprehensive Theory of Obesity and a Healthy Diet: The Causal Role of Oxidative Stress in Food Addiction and Obesity
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-17
    Tobore Onojighofia Tobore

    Background Obesity is a major public health problem whose prevalence has been rapidly increasing in the United States (U.S), and globally. It is one of the leading causes of preventable deaths globally and contributes to the development of many diseases. Methods The search was limited to studies published in English and other languages involving both animal and human subjects. Articles selected included preclinical studies, randomized clinical trials (RCTs), observational studies, meta-analyses, narrative and systemic reviews providing primary quantitative data with a measure of obesity or food addiction as an outcome. Over 5,000 articles were found in the first round of search which was filtered to 506 articles. Results Oxidative stress plays a critical role in food addiction and is both a cause and mediator of obesity. Reactive oxygen species and oxidative stress play a direct role in adipogenesis and modulate all factors involved in obesity including genetics, sleep, gut microbiome, insulin, ghrelin, inflammation, adipokines, leptin, stress, HPA axis, and the hypothalamus. Conclusions The idea of thinking of combating obesity from the lens of calorie count, low carbohydrate, high or low-fat, vegetarian, vegan, plant-based, or animal-based diet is fundamentally wrong. The best way to look at obesity is through the framework of systemic redox homeostasis. Since redox homeostasis is tilted towards increased reactive oxygen species production, and excessive antioxidant intake can result in oxidative stress, an antioxidant and prooxidant food ratio of 2:3 per meal is the ideal nutritional ratio for good health and ideal weight. A ratio of 3:4 is ideal for obese individuals. Regular physical activity, good sleep quality, stress-relieving activities including yoga and meditation, maternal prenatal diet and oxidative stress promoting disease conditions are also important modulators of oxidative stress and obesity.

    更新日期:2020-02-20
  • Parietal alpha-based inhibitory abilities are causally linked to numerosity discrimination
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-17
    Bas Labree; Hannah Corrie; Vyacheslav Karolis; Daniele Didino; Marinella Cappelletti

    Processing numerosities relies on the innate capacity to understand and manipulate the number of items in a set, and to additional abilities such as inhibitory skills –which are known to be linked to brain oscillations in the alpha range. Whether these inhibitory skills are causally linked to numerosity processing and critical for it is unclear. To address this question, we used alpha-based brain stimulation (transcranial alternate current stimulation, tACS) to target inhibitory abilities in the context of numerosity discrimination. Twenty-nine young adults received bilateral tACS to the parietal lobe, a brain region critical for numerical processes. tACS at target (alpha, 10 Hz), control oscillation frequencies (theta, 4 Hz; beta, 22 Hz; sham, no stimulation), and control areas (bilateral frontal regions) was paired to an established numerosity paradigm that allows distinguishing between congruent and incongruent numerosity trials, the latter requiring to inhibit task-irrelevant information. Performance significantly and specifically worsened in incongruent numerosity trials following bilateral parietal alpha-tACS relative to sham and to the other stimulations used, possibly due to the desynchronization of parietal neuronal oscillations in the alpha range. No significant changes in performance were observed in parietal beta and theta-tACS, relative to sham, nor in frontal alpha-tACS. Likewise, there were no changes in performing congruent numerosity trials. We therefore concluded that parietal alpha oscillations are causally linked to inhibitory abilities, and reinforced the view that these abilities are intrinsic to numerosity discrimination.

    更新日期:2020-02-20
  • Administration of a putative pro-dopamine regulator, a neuronutrient, mitigates alcohol intake in alcohol-preferring rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-15
    Naimesh Solanki; Tomilowo Abijo; Carine Galvao; Philippe Darius; Kenneth Blum; Marjorie C. Gondré-Lewis

    Background Excessive alcohol intake is a serious but preventable public health problem in the United States and worldwide. Alcohol and other substance use disorders occur co-morbid with more generalized reward deficiency disorders, characterized by a reduction in dopamine (DA) signaling within the reward pathway, and classically associated with increased impulsivity, risk taking and subsequent drug seeking behavior. It is postulated that increasing dopamine availability and thus restoring DA homeostasis in the mesocorticolimbic system could reduce the motivation to seek and consume ethanol. Here, we treated animals with a neuro-nutrient, KB220Z also known as Synaptamine, designed to augment DA signaling. Method KB220Z was supplied to genetically alcohol-preferring (P) adult male and female rats by oral gavage (PO), intraperioneally (IP), or subcutaneously (SQ) for 4 consecutive days at a 3.4 mL/Kg rat equivalent dose and compared to saline (SQ, IP) or water (PO) controls. Subsequent to treatment, lever pressing and consumption of 10% ethanol, or control 3% sucrose during operant responding was assessed using a drinking in the dark multiple scheduled access (DIDMSA) binge drinking protocol. Locomotor and elevated zero maze activity, and DRD2 mRNA expression via in situ hybridization (ISH) were assessed independently following 4 days of a SQ regimen of KB220Z. Results KB220Z markedly and immediately reduced binge drinking of 10% ethanol in both male and female rats via IP and SC administration whereas P.O. took at least 3 days to decrease lever pressing for ethanol in both male and female rats. There was no effect of SQ KB220Z on 3% sucrose drinking. Elevated activity in the open field was significantly decreased, and time spent in the open arm of the EZM was moderately reduced. The regimen of SQ KB220Z did not impact the number of DRD2 punctae in neurons of the NAc, but NAc-shell expressed more DRD2 mRNA/cell than NAc-core independent of KB220Z. Conclusions KB220Z attenuates drinking and other RDS behaviors in P rats possibly by acting on the dopaminergic system, but not by effecting an increase in NAc DRD2 mRNA expression.

    更新日期:2020-02-20
  • The pesticide fipronil injected into the substantia nigra of male rats decreases striatal dopamine content: a neurochemical, immunohistochemical and behavioral study
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-15
    Rahul Bharatiya; Jessica Bratzu; Carla Lobina; Giulia Corda; Cristina Cocco; Philippe De Deurwaerdere; Antonio Argiolas; Maria Rosaria Melis; Fabrizio Sanna

    Experimental evidence shows that the phenylpyrazole pesticide fipronil exerts neurotoxic effects at central level in rodents, and in particular on nigrostriatal dopaminergic neurons, whose degeneration is well known to cause motor and non-motor deficits in animals and in humans. In order to characterize better the central neurotoxic effect of fipronil, we injected fipronil (15 and 25 µg) dissolved in dimethyl sulfoxide (DMSO) unilaterally into the substantia nigra of male rats. Male rats injected with DMSO unilaterally into the substantia nigra were used as controls. Control and fipronil-treated rats were then tested in different motor (i.e., open field arena, rotarod, tail flick) and non motor tests (novel object recognition, social interaction) 15 days after injection. A systemic challenge dose of the dopamine-agonist apomorphine was also used to study the presence of a rotational behavior. Sixteen days after fipronil or DMSO injection into the substantia nigra, rats were sacrificed, and either striatal dopamine content or substantia nigra tyrosine hydroxylase (TH) immunoreactivity were measured. The results confirm that the unilateral injection of fipronil into the substantia nigra caused the degeneration of nigrostriatal dopaminergic neurons, which leads to a decrease around 50% in striatal dopamine content and substantia nigra TH imunoreactivity. This occurred together with changes in motor activity and coordination, and in nociception but not in recognition memory and in social interaction, as revealed by the results of the behavioral experiments performed in fipronil-treated rats compared to vehicle-treated rats 15 days after treatment, as found with other compounds that destroy nigrostriatal dopaminergic neurons.

    更新日期:2020-02-20
  • Effects of quetiapine on behavioral changes and expression of myelin proteins in a chronic alcohol dependence rat model
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-15
    Jinhong Han; Guodong Wang; Meng Liu; Rui Chai; Jiawei Guo; Feng Zhang; Chengbiao Lu; Yanjie Zhang; Huiying Wang; Ruiling Zhang

    Background As an atypical antipsychotic drug, quetiapine had been approved for bipolar disorder and for adjunctive therapy in major depressive disorder and schizophrenia. Recently quetiapine has been suggested to be a promising pharmacotherapy for alcohol dependence. This study was performed to determine the effects of quetiapine in rats chronically exposed to ethanol. Methods Rats were exposed to ethanol solution (10%; v/v) for 6 weeks. Saline or one of three doses of quetiapine (10, 20 or 40 mg/kg/day) was given by oral gavage while ethanol exposure for the next 14 weeks. Performance of learning and memory and withdrawal signs were evaluated. Then immunohistochemistry, western blot, quantitative real-time-PCR and transmission electron microscopy were performed to determine the effects of quetiapine on alterations of brain white matter markers (myelin basic protein, MBP; proteolipid protein, PLP) and morphology caused by chronic ethanol exposure. Results Quetiapine treatment significantly alleviated withdrawal signs in the ethanol exposed rats. Chronic ethanol exposure reduced Y-type electric maze scores and the protein/mRNA expression levels of MBP and PLP in the prefrontal cortex and hippocampus, and these effects were reversed by quetiapine treatment. Similar ultrastructure morphological changes were observed. Conclusions Chronic quetiapine treatment alleviated the damage induced by chronic ethanol exposure with regard to learning and memory ability and to brain white matter. Thus, quetiapine appears to be a potentially promising pharmacotherapy for the treatment of alcohol use disorder.

    更新日期:2020-02-20
  • Overlap in the neural circuitry and molecular mechanisms underlying ketamine abuse and its use as an antidepressant
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-13
    Saurabh S. Kokane; Ross J. Armant; Carlos A. Bolaños-Guzmán; Linda I. Perrotti

    Ketamine, a dissociative anesthetic and psychedelic compound, has revolutionized the field of psychopharmacology by showing robust, and rapid-acting antidepressant activity in patients suffering from major depressive disorder (MDD), suicidal tendencies, and treatment-resistant depression (TRD). Ketamine’s efficacy, however, is transient, and patients must return to the clinic for repeated treatment as they experience relapse. This is cause for concern because ketamine is known for its abuse liability, and repeated exposure to drugs of abuse often leads to drug abuse/dependence. Though the mechanism(s) underlying its antidepressant activity is an area of current intense research, both clinical and preclinical evidence shows that ketamine’s effects are mediated, at least in part, by molecular adaptations resulting in long-lasting synaptic changes in mesolimbic brain regions known to regulate natural and drug reward. This review outlines our limited knowledge of ketamine’s neurobiological and biochemical underpinnings mediating its antidepressant effects and correlates them to its abuse potential. Depression and addiction share overlapping neural circuitry and molecular mechanisms, and though speculative, repeated use of ketamine for the treatment of depression could lead to the development of substance use disorder/addiction, and thus should be tempered with caution. There is much that remains to be known about the long-term effects of ketamine, and our lack of understanding of neurobiological mechanisms underlying its antidepressant effects is a clear limiting factor that needs to be addressed systematically before using repeated ketamine in the treatment of depressed patients.

    更新日期:2020-02-20
  • Metabolic syndrome accentuates post-traumatic stress disorder-like symptoms and glial activation
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-12
    Ana Cláudia Alves Freire Ribeiro; Tatiane Helena Batista; Viviana Carolina Trujillo Rojas; Alexandre Giusti-Paiva; Fabiana Cardoso Vilela

    The relationship between individuals with post-traumatic stress disorder (PTSD) and the development of metabolic syndrome (MS) is well understood, but the relationship between individuals with preexisting MS and the development of PTSD is not yet known. Therefore, we evaluated the course of PTSD development in preexisting MS rats and we quantified the glial fibrillary acidic protein (GFAP) and ionized the calcium binding adaptor molecule 1 (Iba-1) in the cortex and hippocampus of the experimental animals. Male Wistar rats were divided into two groups: control or 10% fructose for 5 weeks. After 5 weeks of MS induction, a group of animals was used to characterize MS. In another group, after 5 weeks of MS induction, animals were exposed to or not exposed to inescapable footshocks, followed by social isolation. After 14 days of a retention interval, the animals were re-exposed to the inescapable footshocks box, and the freezing time was evaluated. Over the following days, the animals were tested using the open field, social interaction and forced swimming tests, respectively. In another group of animals, after induction of MS and PTSD as previously described, elevated plus maze and object recognition tests were performed. Our results demonstrate that fructose solution for 5 weeks was able to induce MS, and animals with MS had more pronounced PTSD-like symptoms and a greater increase in GFAP and Iba-1 in the hippocampus and prefrontal cortex. In conclusion, MS accentuated PTSD-like symptoms that may be related to increased glial activation. This study helps reveal factors that may predispose individuals to the development of PTSD, such as metabolic disorders.

    更新日期:2020-02-12
  • Improvement of APOE4-dependent non-cognitive behavioural traits by postnatal cholinergic stimulation in female mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-10
    Fiona Peris-Sampedro; Laia Guardia-Escote; Pia Basaure; Maria Cabré; Maria Teresa Colomina

    The apolipoprotein E (APOE) ɛ4 allele hastens cognitive decline, but other non-cognitive behaviours, as well as underpinning interactions with the cholinergic system, have not been systematically addressed. Both C57BL/6 and humanised apoE4 female mice were transiently exposed to subclinical doses (0 or 1 mg/kg body weight) of the cholinesterase inhibitor chlorpyrifos (CPF), a widely-used pesticide, from postnatal days 10 to 15. At 5 months of age, we assessed the impact of APOE4 genotype, postnatal CPF exposure and APOE4 x CPF interactions on anxiety (open field and light-dark tests), stereotypes (digging test) and neophobia (sucrose preference test), as well as on high-fat diet (HFD)-seeking and consumption (scheduled-feeding paradigm). We found that control APOE4 female carriers displayed a robust anxiety-like phenotype, which was accompanied by exaggerated stereotypes and a subtle neophobic response to rewarding foods. In parallel, we observed an amplified “wanting” response for HFD in these mice, which did not entail enhanced “liking”. Notably, postnatal CPF ameliorated the anxiety-like and the heightened HFD-seeking responses in adult apoE4 female mice, while caused them to gain weight steadily compared to control peers. In turn, an early-life transient exposure to CPF fostered the over-consumption of HFD during adulthood without affecting how much this reward was “wanted” or the total caloric intake. These data reveal a role for CPF towards fostering “unhealthy” dietary choices. We conclude that the APOE4 genotype modulates non-cognitive behaviours and we provide support for an APOE4-dependent cholinergic dysfunction.

    更新日期:2020-02-10
  • Optogenetic inactivation of the entopeduncular nucleus improves forelimb akinesia in a Parkinson's disease model
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-10
    Hyung Ho Yoon; Min-Ho Nam; Il Choi; Joongkee Min; Sang Ryong Jeon

    We performed optogenetic inactivation of rats' entopeduncular nucleus (EP, homologous to primates' globus pallidus interna (GPi)) and investigated the therapeutic effect in a rat model of PD. 6-Hydroxydopamine (6-OHDA)-induced hemiparkinsonian rats were injected with either a virus for halorhodopsin expression that is used to inactivate GABAergic neurons or a control virus injection and received optic fiber insertion. All the rats were illuminated by 590 nm of light. Each rat was then subjected to sequential sessions of stepping tests under controlled illumination patterns. The stepping test is a reliable evaluation method for forelimb akinesia. The number of adjusting steps was significantly higher in experimental (optogene with reporter gene expression) (5Hz – 10ms: 15.7 ± 1.9, 5Hz – 100ms: 16.0 ± 1.8, continuous: 21.6 ± 1.9) than control rats (reporter gene expression) (5Hz-10ms: 1.9 ± 1.1, 5Hz-100ms: 2.6 ± 1.0, continuous: 2.5 ± 1.2) (p < 0.001). Continuous EP illumination showed a significantly higher improvement of forelimb akinesia than other illumination patterns (p < 0.01). Optogene expression in the GABAergic neurons of the EP was confirmed by immunohistochemistry. Optogenetic inhibition of EP was effective to improve contralateral forelimb akinesia. However, further studies using prolonged illumination are needed to investigate the best illumination pattern for optogenetic stimulation.

    更新日期:2020-02-10
  • Interaction of COMT and KIBRA modulates the association between hippocampal structure and episodic memory performance in healthy young adults
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-10
    Junxia Wang; Sichu Wu; Yi Sun; Yu Fang; Rui Wu; Jiaming Lu; Zhao Qing; Xue Liang; Zhengge Wang; Wen Zhang; Qian Chen; Ping Cao; Bing Zhang

    Genetic variations of COMT and KIBRA, which were reported to be expressed in the hippocampus, have been linked to memory function. However, their interaction on the hippocampal structure remains unknown. This study aimed to explore the interaction effects of COMT rs4680 and KIBRA rs17070145 on the hippocampal subfield volumes and test their associations with hippocampus-memory relationship in 187 healthy young adults. Two-way analysis of covariance was applied to the alterations in hippocampal subfield volumes among COMT and KIBRA genotypes. Significant interaction effects of these two genes were found in the right CA1 and CA3 subfields. Among KIBRA C-allele carriers, COMT Val/Val homozygotes showed greater volume in these regions than COMT Met-allele carriers. Furthermore, the slope of the correlation between right CA1 volume and immediate recall on the California Verbal Learning Test-II (CVLT-II) (F = 4.36, p = 0.041) as well as CVLT-II delayed recall (F = 6.44, p = 0.014) were significantly different between COMT Val/Val homozygotes and Met-allele carriers, which were positive or tend to be positive in COMT Val/Val group (CVLT immediate recall, r = 0.319, p = 0.040; CVLT delayed recall, r = 0.304, p = 0.051), but absent in COMT Met-allele carriers (CVLT immediate recall, r = -0.263, p = 0.205; CVLT delayed recall, r = -0.351, p = 0.086). These findings may provide a novel insight into the genetic effects upon the hippocampal structure and suggest that the conjoint effects of COMT and KIBRA played a modulatory role in the hippocampus-episodic memory correlation.

    更新日期:2020-02-10
  • First step of odorant detection in the olfactory epithelium and olfactory preferences differ according to the microbiota profile in mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-09
    Laurent Naudon; Adrien François; Mahendra Mariadassou; Magali Monnoye; Catherine Philippe; Aurélia Bruneau; Marie Dussauze; Olivier Rué; Sylvie Rabot; Nicolas Meunier

    We have previously provided the first evidence that the microbiota modulates the physiology of the olfactory epithelium using germfree mice. The extent to which changes to the olfactory system depend on the microbiota is still unknown. In the present work, we explored if different microbiota would differentially impact olfaction. We therefore studied the olfactory function of three groups of mice of the same genetic background, whose parents had been conventionalized before mating with microbiota from three different mouse strains. Caecal short chain fatty acids profiles and 16S rRNA gene sequencing ascertained that gut microbiota differed between the three groups. We then used a behavioural test to measure the attractiveness of various odorants and observed that the three groups of mice differed in their attraction towards odorants. Their olfactory epithelium properties, including electrophysiological responses recorded by electro-olfactograms and expression of genes related to the olfactory transduction pathway, also showed several differences. Overall, our data demonstrate that differences in gut microbiota profiles are associated with differences in olfactory preferences and in olfactory epithelium functioning.

    更新日期:2020-02-10
  • Investigating the role of the amygdala orexin receptor 1 in memory acquisition and extinction in a rat model of PTSD
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-07
    Sudabeh Salehabadi; Kataneh Abrari; Mahmoud Elahdadi Salmani; Meysam Nasiri; Taghi Lashkarbolouki

    Understanding the mechanisms underlying memory is essential for the treatment of post-traumatic stress disorder (PTSD). Orexin, as a lateral hypothalamic (LH) neuropeptide, interferes with the stages of memory, primarily through the orexin receptor1 (Orx1R). The aim of this study was to evaluate the effects of amygdala Orx1R in the acquisition and extinction processes of PTSD modeled in animals. In three experiments, rats were divided into three groups: control (Naïve), shock (receiving a foot shock), and PTSD (experiencing Single prolonged stress (SPS) method). The first experiment aimed to evaluate LH activity in PTSD modeled rats. The second and third experiments aimed to evaluate the effects of Orx1R in the acquisition and extinction of fear memory in PTSD modeled animals. SB334867 (SB) or its solvent was microinjected into the amygdala and the rats were subjected to conditioning thereafter. In the second group, we used a single injection after conditioning. In the third group, we used three consecutive injections (one after each memory test). Some behaviors and Orx1R expression were evaluated. The freezing response was significantly longer in the PTSD group than on the control. Similarly, anxiety and sensitized fear were also intensified. CFos expression levels in LH was higher in the PTSD group. Inhibition of Orx1R in the amygdala significantly decreased memory acquisition, diminished anxiety, and decreased the sensitized fear in the SB group. Applying SB to the amygdala after each fear memory test significantly decreased freezing. Expression of Orx1R was significantly higher following fear conditioning. These results indicate a likely involvement of the orexin and amygdalar Orx1R in memory acquisition and in extinction of PTSD.

    更新日期:2020-02-07
  • Neuroscience of the auditory-motor system; How does sound interact with movement?
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-07
    C. Lezama-Espinosa; H.L. Hernández-Montiel

    Human musicality is a complex problem because it involves the coupling of multiple exogenous and endogenous signals with different physical properties. The synchronization of these signals translates into specific behaviors. The study of this synchronization, based on the physical properties of two oscillatory bodies, is the first step in understanding the behaviors associated with rhythmic auditory stimuli. In recent years, different neurorehabilitation therapies have emerged for motor pathologies involving music. However, the neurophysiological bases that describe the coupling phenomenon are not yet fully understood. In this article, two theories are addressed that attempt to explain the convergence of the auditory system and the motor system according to new neuroanatomical, neurophysiological and artificial neural network findings. It also reflects on the different approaches to a complex problem in cognitive neuroscience and the need for a study model for the different motor behaviors evoked by auditory stimuli.

    更新日期:2020-02-07
  • Dietary intake of polyunsaturated fatty acids alleviates cognition deficits and depression-like behaviour via cannabinoid system in sleep deprivation rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-06
    Tiandong Wang; Kang Niu; Anni Fan; Nanxi Bi; Han Tao; Xiang-Tao Chen; Hui-Li Wang

    Sleep deprivation (SD) is a common feature in modern society. Prolonged sleep deprivation causes cognition deficits and depression-like behavior in the model of animal experiments. Endocannabinoid system are key modulators of synaptic function, which were related to memory and mood. Although the underlying mechanism remains unknown, several studies indicated the benefits of polyunsaturated fatty acids (PUFAs, linolenic acid, 39.7%; linoleic acid, 28%; and oleic acid, 22%) on brain function through the endocannabinoid system. The present study aimed to evaluate the influence of dietary PUFAs on cognition deficits induced by sleep deprivation in Sprague Dawley rats. The rats were sleep deprivation continuously for 7 days and fed with PUFAs at three different dosages (2, 4 and 8 μl/g body weight) at the meantime. The effect of PUFAs on cognition was investigated by object recognition test while depressive-like behavior were detected using sucrose preference test and forced swim test. The mechanism of PUFAs was elucidated by hippocampal synaptic transmission analyses. The resluts revealed that SD led to the disorder of cognition and mood which was improved by the supplement of PUFAs. SD significantly increased the mEPSC frequency, and decreased the protein level of cannabinoid type-1 receptors (CB1R). These changes were restored by supplement of PUFAs, which showed a similar level to the control group. Behaviour tests showed that the positive effects on repairing cognition and anxiety disorders were almost completely abolished when the CB1R receptor antagonist rimonabant was applied to the SD rats. These findings indicated that PUFAs are a factor regulating cognition deficits and depression induced by SD via cannabinoid type-1 receptors.

    更新日期:2020-02-07
  • Brain activity underlying American crow processing of encounters with dead conspecifics
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-06
    Kaeli N. Swift; John M. Marzluff; Christopher N. Templeton; Toru Shimizu; Donna J. Cross

    Animals utilize a variety of auditory and visual cues to navigate the landscape of fear. For some species, including corvids, dead conspecifics appear to act as one such visual cue of danger, and prompt alarm calling by attending conspecifics. Which brain regions mediate responses to dead conspecifics, and how this compares to other threats, has so far only been speculative. Using 18F-fluorodeoxyglucose positron emission tomography (FDG-PET) we contrast the metabolic response to visual and auditory cues associated with a dead conspecific among five a priori selected regions in the American crow (Corvus brachyrhynchos) brain: the hippocampus, nidopallium caudolaterale, striatum, amygdala, and the septum. Using a repeated-measures, fully balanced approach, we exposed crows to four stimuli: a dead conspecific, a dead song sparrow (Melospiza melodia), conspecific alarm calls given in response to a dead crow, and conspecific food begging calls. We find that in response to observations of a dead crow, crows show significant activity in areas associated with higher-order decision-making (NCL), but not in areas associated with social behaviors or fear learning. We do not find strong differences in activation between hearing alarm calls and food begging calls; both activate the NCL. Lastly, repeated exposures to negative stimuli had a marginal effect on later increasing the subjects’ brain activity in response to control stimuli, suggesting that crows might quickly learn from negative experiences.

    更新日期:2020-02-07
  • Resting-State Functional Connectivity of the Anterior Cingulate Cortex in Young Adults Depressed Patients with and without Suicidal Behavior
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-05
    Haitang Qiu; Bo Cao; Jun Cao; Xinke Li; Jianmei Chen; Wo Wang; Zhen Lv; Shuang Zhang; Weidong Fang; Ming Ai; li Kuang

    Functional alterations in the subregions of the anterior cingulate cortex (ACC) have been observed in patients with major depressive disorder (MDD). Studies have shown that higher depressive symptoms are associated with altered functional connectivity (FC) in different ACC sub-regions. Suicide is highly prevalent in patients with MDD; however, it is unclear whether suicidal behavior is associated with the FC alterations in the subregions of the ACC in these indibiduals. Seventy-six patients with MDD (41 with and 35 without a history of suicidal behavior) underwent functional magnetic resonance imaging (fMRI) and were assessed using the Hamilton Rating Scale for Depression (HAMD), the Scale for Suicide Ideation (SSI), and the Columbia Scale for Rating of Suicide Severity. We investigated the FC between the ACC subregions and other brain regions in young MDD patients with and without a history of suicidal behavior. The FC in the subregions of the ACC-superior frontal gyrus differed significantly between the two groups. Additionally, the anterior sgACC-right caudate FC and the pgACC-left insula FC were found to be abnormal in the suicidal MDD group. Interestingly, the suicidal ideation score positively correlated with decreased FC in the pgACC-superior frontal gyrus in both groups, but it negatively correlated with increased FC in the anterior sgACC-superior frontal gyrus in the non-suicidal MDD group. Our findings indicate that altered connections of subregions in the ACC may be involved in the neurological mechanisms underlying suicide in young adults with MDD.

    更新日期:2020-02-06
  • Focused-attention meditation increases cognitive control during motor sequence performance: Evidence from the N2 cortical evoked potential
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-04
    Russell W. Chan; Phillip M. Alday; Lena Zou-Williams; Kurt Lushington; Matthias Schlesewsky; Ina Bornkessel-Schlesewsky; Maarten A. Immink
    更新日期:2020-02-04
  • Disturbance of taste reactivity and other behavioral alterations after bilateral interleukin-1β microinjection into the cingulate cortex of the rat
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-04
    Bettina Réka László; Edina Hormay; István Szabó; Kitti Mintál; Bernadett Nagy; Kristóf László; László Péczely; Tamás Ollmann; László Lénárd; Zoltán Karádi

    The anterior cingulate cortex (ACC), is known to be intimately involved in food-related motivational processes and their behavioral organization, primarily by evaluating hedonic properties of the relevant stimuli. In the present study, the involvement of cingulate cortical interleukin-1β (IL-1β) mediated mechanisms in a) gustation associated facial and somato-motor behavioral patterns of Wistar rats were examined in taste reactivity test (TR). In addition, b) conditioned taste aversion (CTA) paradigm was performed to investigate the role of these cytokine mechanisms in taste sensation associated learning processes, c) the general locomotor activity of the animals was observed in open field test (OPF), and d) the potentially negative reinforcing effect of IL-1β was examined in conditioned place preference test (CPP). During the TR test, species specific behavioral patterns in response to the five basic tastes were analyzed. Response rates of ingestive and aversive patterns of the cytokine treated and the control groups differed significantly in case of the weaker bitter (QHCl, 0.03 mM), and the stronger umami (MSG, 0.5 M) tastes. IL-1β itself did not elicit CTA, it did not interfere with the acquisition of LiCl induced CTA, and it also failed to cause place preference or aversion in the CPP test. In the OPF paradigm, however, significant differences were found between the cytokine treated and the control groups in the rearing and grooming, the number of crossings, and in the distance moved. Our results indicate the involvement of cingulate cortical IL-1β mechanisms in the control of taste perception and other relevant behavioral processes.

    更新日期:2020-02-04
  • Anti-neuroinflammatory effects of dimethylaminomylide (DMAMCL, i.e., ACT001) are associated with attenuating the NLRP3 inflammasome in MPTP-induced Parkinson disease in mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-04
    Qianqian Liu; Xinyang Guo; Ziwei Huang; Qiujia He; Dashuai Zhu; Shaozhi Zhang; Ziwei Peng; Yongzhe Che; Xizeng Feng

    Parthenolide (PTL) is a natural compound with anti-inflammatory and antioxidant properties and is an active ingredient extracted from the medicinal plant Tanacetum parthenium. ACT001 is derived from parthenolide and is a fumarate form of dimethylaminomylide (DMAMCL). Its effect is equivalent to that of PTL, but it is more stable in plasma and has lower acquisition costs. Related reports indicate that NLRP3-mediated neuroinflammation is involved in the progression of Parkinson's disease (PD). In our research, we explored whether ACT001 alleviates NLRP3-mediated neuroinflammation in PD mice induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Our results revealed that ACT001 reduces movement impairment and cognitive deficit in PD mice. In addition, it alleviates dopaminergic neurodegeneration in the nigrostriatal pathway and inhibits oxidative stress, the inflammatory response and activation of the NLRP3 inflammasome in the midbrain of MPTP-induced PD mice. Moreover, it attenuates microglial activation in the nigrostriatal pathway. Overall, our study showed that ACT001 alleviates NLRP3-mediated neuroinflammation in PD mice induced by MPTP.

    更新日期:2020-02-04
  • A Mouse Model of Chemotherapy-Related Cognitive Impairments Integrating the Risk Factors of Aging and APOE4 Genotype
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-03
    Tamar C. Demby; Olga Rodriguez; Camryn W. McCarthy; Yi-Chien Lee; Christopher Albanese; Jeanne Mandelblatt; G. William Rebeck

    Some cancer survivors experience marked cognitive impairment, referred to as cancer-related cognitive impairment (CRCI). CRCI has been linked to the genetic factor APOE4, the strongest genetic risk factor for Alzheimer’s disease (AD). We used APOE knock-in mice to test whether the relationship between APOE4 and CRCI can be demonstrated in a mouse model, to identify associations of chemotherapy with behavioural and structural correlates of cognition, and to test whether chemotherapy affects markers of AD. Twelve-month old C57BL/6 J female APOE3 (n = 30) and APOE4 (n = 31) knock-in mice were randomized to treatment with either doxorubicin (10 mg/kg) or saline. Behavioural assays at 2-21 weeks-post exposure included open field maze, elevated zero maze, pre-pulse inhibition, Barnes maze, and fear conditioning. Ex-vivo magnetic resonance imaging was used to determine regional volume differences at 31-35 weeks-post exposure, and tissue sections were analyzed for markers of AD pathogenesis. Minimal toxicities were observed in the aged mice after doxorubicin exposure. In the Barnes maze assay, APOE3 mice did not exhibit impairment in spatial learning after doxorubicin treatment, but APOE4 mice demonstrated significant impairments in both the initial identification of the escape hole and the latency to full escape at 6 weeks post-exposure. Both APOE3 and APOE4 mice treated with doxorubicin showed impairment of spatial memory. Grey matter volume in the frontal cortex decreased in APOE4 mice treated with doxorubicin vs. APOE3 mice. This study demonstrates cognitive impairments in aged APOE4 knock-in mice after doxorubicin treatment and establishes this system as a novel and powerful model of CRCI.

    更新日期:2020-02-03
  • Type 3 adenylyl cyclase in the MOE is involved in learning and memory in mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-02
    Xinxia Liu; Yanfen Zhou; Dong Yang; Shujuan Li; Xiaodong Liu; Zhenshan Wang

    Although olfactory dysfunction is related to learning and memory impairment, the causal relationship between main olfactory epithelium (MOE) disruption and learning and memory is still unknown. The present study aimed to establish whether MOE disruption causes learning and memory impairment and whether the expression of type 3 adenylyl cyclas (AC3) in the MOE is related to learning and memory. First, the buried food test was carried out to confirm that MOE function was disrupted in mice treated with nasal instillation of zinc sulfate (ZnSO4 mice), and mice with specific knockdown of AC3 in the MOE by CRISPR/Cas9 technology (AC3KD/MOE mice). Then, behavioural tasks associated with learning and memory were administered. ZnSO4 mice and AC3KD/MOE mice showed impairments in learning and memory tests, including the novel object recognition test, the step-down passive avoidance test, the Morris water maze test, and the Y-maze test. Our data demonstrate that MOE disruption caused by nasal exposure to ZnSO4 or specific knockdown of AC3 in the MOE resulted in learning and memory impairment, and they further demonstrate that the expression of AC3 in the MOE plays a major role in learning and memory.

    更新日期:2020-02-03
  • Mechanisms of a near-orthogonal ultra-fast evolution of human behaviour as a source of culture development
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-02
    Christian P. Müller

    Current human culture is characterized by an increasing rate of accumulating potential and actually performed behaviours. The growth of behavioural complexity as well as the ex-vivo accumulation of human behaviour, here identified as the non-genetically inherited (NGI) behaviourome, cannot be explained by genetic/epigenetic mechanisms of inheritance. As human beings derive their socio-cultural identity predominantly from their behaviourome, mechanisms of heritability should predominantly consider inheritance and accumulation of the NGI behaviourome. Here we propose key mechanisms of a near-orthogonal and ultra-fast evolution of the NGI human behaviourome that provide a foundation not only of unique human culture development, but also of its recent acceleration. Thereby, the evolution of the human NGI behaviourome underlies similar features as genetically based evolution. However, specific mechanisms of mutation and selection work largely independent (orthogonal) from genetic/epigenetic mechanisms. We suggest a mechanism of how adaptive changes (mutations) in the NGI behaviourome work target-directed and how selection works on an ultra-fast time scale. Selection results are mostly not fatal for the individual which allows for a much increased mutation rate. For crucial accumulation of the NGI behaviourome, ex-vivo storage and retrieval systems of virtually unlimited capacity are described. We discuss the great potential of the human NGI behaviourome in respect of speculative human super-reproduction and homosexual reproduction success, as well as a possible unique human way to avoid reproduction failure in childlessness. Altogether, this model of human behavioural reproduction and accumulation of behaviour may provide a base for better understanding and prediction of uniquely human cultural development.

    更新日期:2020-02-03
  • Ketamine: Leading us into the future for development of antidepressants
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-02
    Flavia R. Carreno; Daniel J. Lodge; Alan Frazer

    Numerous randomized double-blind clinical trials have consistently shown that that a single intravenous administration of a subanesthetic dose of ketamine to treatment-resistant depressed patients significantly improved depressive symptomatology rapidly, within two hours, with the effect lasting up to seven days. Despite its very promising effects, ketamine has long been associated with potential for abuse as it can cause psychotropic side effects, such as hallucinations, false beliefs, and severe impairments in judgment and other cognitive processes. Consequently, within the last two decades preclinical research has been carried out aimed at understanding its mechanisms of action and the brain circuits involved in ketamine’s antidepressant effects, both of which are discussed in this review. Furthermore, with the hippocampus being a key target for ketamine’s beneficial antidepressant effects, we and others have begun to examine behavioral and neurochemical effects of drugs that act selectively on the hippocampus due to the preferential location of their receptor targets. Such drugs are negative allosteric modulators (NAMs) and positive allosteric modulator (PAM) of the α5-GABAA receptor. Such compounds are discussed within the framework of how lessons learned with ketamine point to novel classes of drugs, targeting the GABAergic system, that can recapitulate the antidepressant effects of ketamine without its adverse effects.

    更新日期:2020-02-03
  • Ketamine: The final frontier or another depressing end?
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-02-01
    Omar K. Sial; Eric M. Parise; Lyonna F. Parise; Tamara Gnecco; Carlos A. Bolaños-Guzmán

    Two decades ago, the observation of a rapid and sustained antidepressant response after ketamine administration provided an exciting new avenue in the search for more effective therapeutics for the treatment of clinical depression. Research elucidating the mechanism(s) underlying ketamine’s antidepressant properties has led to the development of several hypotheses, including that of disinhibition of excitatory glutamate neurons via blockade of N-methyl-D-aspartate (NMDA) receptors. Although the prominent understanding has been that ketamine’s mode of action is mediated solely via the NMDA receptor, this view has been challenged by reports implicating other glutamate receptors such as AMPA, and other neurotransmitter systems such as serotonin and opioids in the antidepressant response. The recent approval of esketamine (Spravato™) for the treatment of depression has sparked a resurgence of interest for a deeper understanding of the mechanism(s) underlying ketamine’s actions and safe therapeutic use. This review aims to present our current knowledge on both NMDA and non-NMDA mechanisms implicated in ketamine’s response, and addresses the controversy surrounding the antidepressant role and potency of its stereoisomers and metabolites. There is much that remains to be known about our understanding of ketamine’s antidepressant properties; and although the arrival of esketamine has been received with great enthusiasm, it is now more important than ever that its mechanisms of action be fully delineated, and both the short- and long-term neurobiological/functional consequences of its treatment be thoroughly characterized.

    更新日期:2020-02-03
  • Early weaning leads to disruption of homeostatic and hedonic eating behaviors and modulates Serotonin (5 H T) and Dopamine (DA) systems in male adult rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-31
    Gabriel Araújo Tavares; Larissa Cavalcanti do Amaral Almeida; Julliet Araújo de Souza; Victor Vasconcelos de Farias; Felipe Leitão de Souza; Severina Cassia de Andrade Silva; Claudia Jacques Lagranha; Bertrand Kaeffer; Sandra Lopes de Souza

    Early weaning is associated with disruption of eating behavior. However, little is known about the mechanisms behind it. 5 H T and DA systems are key regulators of homeostatic and hedonic eating behaviors, respectively. Thus, this study aims to evaluate the effects of early weaning on feeding behavior and 5 H T and DA systems. For this, rats were submitted to regular (PND30) or early weaning (PND15) and between PND250 and PND300 were evaluated food intake of standard diet in response to 4 h food deprivation, during the 24 h period and per phase of the circadian cycle, in addition to the palatable food intake. Additionally, body mass and mRNA expression of 5 H T1B, 5 H T2C, SERT, DRD1 and DRD2 were evaluated in the hypothalamus and brainstem. The results demonstrate that early weaning promoted an increase in standard food intake in response to a 4 h food deprivation in the 24 h period and in the dark phase of the circadian cycle, in addition to an increased palatable food intake. No differences in body mass between regular or early weaning were observed. In the hypothalamus, increased mRNA expression of SERT and DRD1 was observed, but decreased 5 H T1B mRNA expression. In the brainstem, the expression of 5 H T1B, SERT, 5 H T2C, DRD1 and DRD2 was increased in early weaned rats. In a nutshell, the stress promoted by early weaning has programmed the animals to be hyperphagic and to increase their palatable food intake, which was associated with modulation of 5 H T and DA systems.

    更新日期:2020-01-31
  • Anxiolytic-like effects of the ethanol extract of Magnolia obovata leaves through its effects on GABA-benzodiazepine receptor and neuroinflammation
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-30
    Hyeon Joo Ham; Yong Sun Lee; Jaesuk Yun; Sang-Bae Han; Dong Ju Son; Jin Tae Hong

    Recently, there have been studies that examined the relationship between neuroinflammation and anxiety disorder. Herein, we investigated the anxiolytic effect of a well-studied medicinal plant with anti-inflammatory properties, Magnolia obovata, by conducting cellular and animal studies. At the cellular level, the ethanol extract of M. obovata leaves demonstrated inhibitory effects on the production of nitric oxide and inflammatory cytokines and proteins in cultured BV-2 cells. The extract also enhanced GABA-benzodiazepine receptor activity by increasing chloride ion influx in primary cultured neuronal cells. We also examined the anxiolytic effect of the extract in imprinting control region male mice by conducting several behavioral tests. The mice were administered daily oral dose of M. obovata extract (25 mg/kg and 50 mg/kg) for 2 weeks. The extract increased the number of entries and time spent in open arms in the elevated plus maze test and decreased locomotor activity in the spontaneous locomotor activity test, thus implying that the extract ameliorated anxiety levels in mice. Furthermore, we found that the extract inhibited the expression of inflammatory proteins and cytokines and enhanced the expression of GABA-benzodiazepine receptor. These results suggest that the ethanol extract of M. obovata leaves may have an anxiolytic effect through enhancement of the GABAergic system and anti-neuroinflammatory mechanisms.

    更新日期:2020-01-31
  • H2S prevents injury after ischemic stroke by diminishing the assembly of CaMKII with ASK1-MKK3-p38 signaling module
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-30
    Yuan-Jian Song; Yue Shi; Miaomiao Cui; Man Li; Xiang-Ru Wen; Xiao-Yan Zhou; He-Qing Lou; Yu-Lan Wang; Da-Shi Qi; Man Tang; Xun-Bao Zhang

    Cerebral ischemia/reperfusion (I/R) injury is a leading cause of learning and memory dysfunction. Hydrogen sulfide (H2S) has been shown to confer neuroprotection in various neurodegenerative diseases, including cerebral I/R-induced hippocampal CA1 injury. However, the underlying mechanisms have not been completely understood. In the present study, rats were pretreated with SAM/NaHS (SAM, an H2S agonist, and NaHS, an H2S donor) only or SAM/NaHS combined with CaM (an activator of CaMKII) prior to cerebral ischemia. The Morris water maze test demonstrated that SAM/NaHS could alleviate learning and memory impairment induced by cerebral I/R injury. Cresyl violet staining was used to show the survival of hippocampal CA1 pyramidal neurons. SAM/NaHS significantly increased the number of surviving cells, whereas CaM weakened the protection induced by SAM/NaHS. The immunohistochemistry results indicated that the number of Iba1-positive microglia significantly increased after cerebral I/R. Compared with the I/R group, the number of Iba1-positive microglia in the SAM/NaHS groups significantly decreased. Co-Immunoprecipitation and immunoblotting were conducted to demonstrate that SAM/NaHS suppressed the assembly of CaMKII with the ASK1-MKK3-p38 signal module after cerebral I/R, which decreased the phosphorylation of p38. In contrast, CaM significantly inhibited the effects of SAM/NaHS. Taken together, the results suggested that SAM/NaHS could suppress cerebral I/R injury by downregulating p38 phosphorylation via decreasing the assembly of CaMKII with the ASK1-MKK3-p38 signal module.

    更新日期:2020-01-31
  • 5-HT1A and α2 adrenergic receptor levels are associated with high anxiety-like patterns and impulsivity in selectively bred Long Evans rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-30
    Tim Niedzielak; Rebecca Ravenelle; Marie Joseph; Corey Calhoun; Brooke Plotkin; Raquel Jones; Maria Herrera; S. Tiffany Donaldson
    更新日期:2020-01-31
  • Temporal development of neurochemical and cognitive impairments following reserpine administration in rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-30
    Aline Guimarães Pereira; Anicleto Poli; Filipe Carvalho Matheus; Lucila de Bortoli da Silva; Guilherme Pasetto Fadanni; Geison Souza Izídio; Alexandra Latini; Rui Daniel Prediger

    The systemic administration of low reserpine (RES) doses (0.1 – 1.0 mg/kg) has been proposed as a valuable rat model for the study of non-motor symptoms of Parkinson’s disease (PD). Here, we investigated the temporal-dependent effects of RES (1 mg/kg, s.c.) on short-term memory and locomotion, as well as, the levels of dopamine, serotonin and its metabolites in the striatum, hippocampus and prefrontal cortex at 3, 24 or 72 h after RES administration. RES administrations resulted in social and object recognition memory impairment and increased dopamine turnover in the striatum, without changes in the rat spontaneous locomotor activity, 3 h after RES administration. Altogether, these results provide new insights for the use of RES administration as an experimental design for the study of PD non-motor symptoms in rats.

    更新日期:2020-01-31
  • Chronic Unpredictable Intermittent Restraint Stress Disrupts Spatial Memory in Male, but not Female Rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-30
    Dylan N. Peay; Hovhannes M. Saribekyan; Priscilla A. Parada; Elizabeth M. Hanson; Bryce S. Badaruddin; Jessica M. Judd; Megan E. Donnay; Diego Padilla-Garcia; Cheryl D. Conrad

    Chronic stress leads to sex-dependent outcomes on spatial memory by producing deficits in males, but not in females. Recently it was reported that compared to daily restraint, intermittent restraint (IR) produced more robust stress and anxiety responses in male rats. Whether IR would be sufficiently robust to impair hippocampal-dependent spatial memory in both male and female rats was investigated. IR involved mixing restraint with non-restraint days over weeks before assessing spatial memory and anxiety profile on the radial arm water maze, object placement, novel object recognition, Y-maze, open field and novelty suppressed feeding. Experiments 1 and 2 used Sprague-Dawley male rats only and determined that IR for 6 hrs/d (IR6), but not 2 hrs/d, impaired spatial memory and that task order was important. In experiment 3, IR6 was extended for 6wks before spatial memory testing commenced using both sexes. Unexpectedly, an extended IR6 paradigm failed to impair spatial memory in either sex, suggesting that by 6wks IR6 may have become predictable. In experiment 4, an unpredictable IR (UIR) paradigm was implemented, in which restraint duration (30 or 60-min) combined with orbital shaking, time of day, and the days off from UIR were varied. UIR impaired spatial memory in males, but not in females. Together with other reports, these findings support the interpretation that chronic stress negatively impairs hippocampal-dependent function in males, but not in females. We interpret these findings to show that females are more resilient to chronic stress than are males as it pertains to spatial ability.

    更新日期:2020-01-31
  • Physical exercise rectifies CUMS-induced aberrant regional homogeneity in mice accompanied by the adjustment of skeletal muscle PGC-1a/IDO1 signals and hippocampal function
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-30
    Zhaoyang Dong; Zhi Liu; Ye Liu; Rong Zhang; Haixin Mo; Lei Gao; Yafei Shi

    Background Depression is a debilitating condition with a profound influence on quality of life for millions of people globally. Physical exercise has been broadly recognized for its therapeutic effects on depression, but the mechanisms that underlie its benefits remain unknown. In the study, we investigated whether the physical exercise of could be a protection from stress-induced depression and its impact on the brain activity of Regional Homogeneity (ReHo) in mice. Methods Adult male C57BL/6 mice were assigned to one of the following groups: control group; exercise group, 2 hours/day in a running wheel apparatus; chronic unpredictable mild stress (CUMS) group; CUMS + exercise group. rs-fMRI was applied to detect the changes of regional spontaneous activity. Results Firstly, CUMS-induced depressive behavior was significantly reduced by exercise. Base on the ReHo analysis, disorders of the regional spontaneous activity in the brain of CUMS mice, primarily in the limbic system, especially in the hippocampus and PFC, motor cortex, sensory cortex, visual cortex were found. While exercise remarkably prevented the CUMS-induced chaos of brain activity in parts of the above regions, such as cortex, hippocampus and corpus callosum. These results suggested physical exercise could prevent the dysfunction of mood-regulating circuit in CUMS model. Furthermore, exercise improved skeletal muscle PGC-1a and hippocampal BDNF levels in stress mice, and reduced IDO1 in skeletal muscle. Conclusions These results suggested that exercise prevented CUMS induced depressive behaviors and brain regional spontaneous activity in mice, accompanied with the adjustment of skeletal muscle PGC-1a/IDO1 signals and hippocampal function.

    更新日期:2020-01-31
  • A proteomic signature for CNS adaptations to the valence of environmental stimulation
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-29
    Andrew Shaw; Luke D Arnold; Lucia Privitera; Phillip D Whitfield; Mary K Doherty; Lorenzo Morè
    更新日期:2020-01-30
  • Rapid effects of estradiol and its receptors on object recognition and object placement in adult male zebrafish
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-28
    Mohammad Naderi; Arash Salahinejad; Anoosha Attaran; Som Niyogi; Douglas P. Chivers

    In recent years, there has been a growing appreciation that 17β-estradiol (E2) can rapidly modulate learning and memory processes by binding to membrane estrogen receptors and cause the activation of a number of signaling cascades within the central nervous system. In this study, we sought to investigate the effects of post-training administration of E2 (100 ng/g, 1 µg/g, 10 µg/g) and involvement of the estrogen receptors (ERs) using selective ER agonists on the consolidation of object recognition (OR) and object placement memory (OP) in adult male zebrafish. The general activation of ERs with the highest E2 dose improved consolidation of memory in both learning tasks within 1.45 h of administration. Activation of classical ERs (ERα and ERβ) improved consolidation of OR memory, but had no effect on fish performance in OP task. On the other hand, activation of G protein-coupled ER1 impaired and enhanced consolidation of OR and OP memories, respectively. Memory improvement in both tasks was accompanied by a marked up-regulation in the expression of genes encoding ionotropic and metabotropic glutamate receptors in a task-dependent manner. In contrast, the down-regulation in the expression of certain ionotropic glutamate receptors was observed in fish with impaired OR memory. Moreover, our study also revealed an increase in the transcript abundance of genes associated with synaptic protein synthesis (brain-derived neurotrophic factor, synaptophysin, and the mechanistic target of rapamycin). These results suggest that E2 may affect consolidation of memory in zebrafish likely through rapid changes in synaptic morphology and function.

    更新日期:2020-01-30
  • Exercise effects on brain and behavior in healthy mice, Alzheimer’s disease and Parkinson’s disease model - a systematic review and meta-analysis
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-25
    Thiago Medeiros da Costa Daniele; Pedro Felipe Carvalhedo de Bruin; Robson Salviano de Matos; Gabriela Sales de Bruin; Cauby Maia Chaves Junior; Veralice Meireles Sales de Bruin

    This systematic review and meta-analysis examines how exercise modifies brain and behavior in healthy mice, dementia (D) and Parkinson disease (PD) models. A search was performed on the Medline and Scopus electronic databases (2008 to 2019). Search terms were “mice”, “brain”, “treadmill”, “exercise”, “physical exercise”. In the total, 430 were found but only 103 were included. Animals (n = 1,172; 96 articles) exercised 4-8 weeks (Range 24 h to 32 weeks), 60 min/day (Range 8 to 120 min per day), and 10/12 m/min (Range 0.2 m/min to 36 m/min). Hippocampus, cerebral cortex, striatum and whole brain were more frequently investigated. Exercise improved learning and memory. Meta-analysis showed that exercise increased: cerebral BDNF in health (n = 150; z = 5.8, CI 3.43-12.05; p < 0.001 I2 = 94.3%), D (n = 124; z = 4.18, CI = 2.22-9.12; p < 0.001; I2 = 93.7%) and PD (n = 16 z = 4.26, CI 5.03-48.73 p < 0.001 I2 = 94.8%). TrkB improved in health (n = 84 z = 5.49, CI 3.8-17.73 p < 0.001, I2 = 0.000) and PD (n = 22; z = 3.1, CI = 2.58-67.3, p < 0.002 I2 = 93.8%). Neurogenesis increased in health (n = 68; z = 7.08, CI 5.65-21.25 p < 0.001; I2 17.58) and D model (n = 116; z = 4.18, CI 2.22-9.12 p < 0.001 I2 93.7%). Exercise augmented amyloid clearance (n = 166; z = 7.51 CI = 4.86-14.85, p < 0.001 I2 = 58.72) and reduced amyloid plaques in D models (n = 49; z = 4.65, CI = 3.94-15.3 p < 0.001 I2 = 0.000). In conclusion, exercise improved brain and behavior, neurogenesis in healthy and dementia models, reduced toxicity and cerebral amyloid. Evidence regarding inflammation, oxidative stress and energy metabolism were scarce. Studies examining acute vs chronic exercise, extreme training and the durability of exercise benefit were rare. Vascular or glucose metabolism changes were seldom reported.

    更新日期:2020-01-26
  • Attention bias towards threat in African American children exposed to early life trauma
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-25
    Maya Lakshman; Lauren Murphy; Yara Mekawi; Sierra Carter; Maria Briscione; Bekh Bradley; Erin B. Tone; Seth D. Norrholm; Tanja Jovanovic; Abigail Powers

    Background Attentional bias is linked to a range of mood disorders, including posttraumatic stress disorder (PTSD). The present study examined attention bias patterns in African American children exposed to trauma, in order to better understand potential risk factors for PTSD. Methods 31 children (ages 8–14) completed an eye-tracking task to assess gaze bias patterns while viewing pairs of emotional and neutral faces. Trauma exposure and PTSD symptoms were assessed in a subsample of children (n = 24). Results Repeated measures analysis of variance (ANOVA) results examining attention bias indices and gender showed greater attention bias toward angry faces than happy faces (p < 0.01) and toward emotional faces in males than females (p < 0.05). Correlational analyses showed attention bias toward angry faces was associated with greater levels of child trauma exposure (p < 0.05). Based on linear regression analysis, child trauma exposure accounted for 17 % of variance in attention bias toward angry versus neutral faces independent of gender or posttraumatic stress symptoms (p < 0.05). Conclusions Trauma exposure in children is related to altered attention bias, via enhanced attention towards threatening cues. Results contribute to evidence that males and females may exhibit different attentional patterns. This study highlights the importance of additional research on attention bias patterns and prospective mental health outcomes across gender and through development.

    更新日期:2020-01-26
  • The protective and therapeutic effects of vinpocetine, a PDE1 inhibitor, on oxidative stress and learning and memory impairment induced by an intracerebroventricular (ICV) injection of amyloid beta (Aβ) peptide
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-25
    Meysam Shekarian; Alireza Komaki; Siamak Shahidi; Abdolrahman Sarihi; Iraj Salehi; Safoura Raoufi

    Alzheimer’s disease (AD) is a neurodegenerative disease leading to cognitive and memory impairment. This study aimed at investigating the therapeutic and preserving effects of vinpocetine on amyloid beta (Aβ)-induced rat model of AD. Sixty male adult Wistar rats were randomly divided into 6 groups (n = 10 per group) as follows: 1; control, 2; sham, 3; Aβ, 4; pre-treatment (vinpocetine + Aβ): oral gavage administration of vinpocetine at 4 mg/kg for 30 days followed by intracerebroventricular (ICV) injection of Aβ, 5; treatment (Aβ + vinpocetine): Aβ ICV injection followed by vinpocetine administration for 30 days, 6; pre-treatment + treatment (vinpocetine + Aβ + vinpocetine): vinpocetine administration for 30 days before and 30 days after AD induction. Following treatments, the animals’ learning and memory were investigated using passive avoidance learning (PAL) task, Morris water maze (MWM), and novel object recognition (NOR) tests. The results demonstrated that Aβ significantly enhanced escape latency and the distance traveled in the MWM, decreased step-through latency, and increased time spent in the dark compartment in PAL. Vinpocetine ameliorated the Aβ-infused memory deficits in both MWM and PAL tests. Administration of vinpocetine in the Aβ rats increased the discrimination index of the NOR test. It also significantly diminished the nitric oxide and malondialdehyde levels and restored the reduced glutathione (GSH) levels. Vinpocetine can improve memory and learning impairment following Aβ infusion due to its different properties, including antioxidant effects, which indicates that vinpocetine administration can lead to the amelioration of cognitive dysfunction in AD.

    更新日期:2020-01-26
  • Endocannabinoids mediate long-lasting behavioural and physiological changes in male rats induced by the repeated activation of the mesolimbic system by copulation to satiety
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Estefanía González-Morales; Gabriela Rodríguez-Manzo

    Sexually satiated male rats exhibit long-lasting physiological changes, suggestive of brain plasticity, the most conspicuous of which are a sexual behaviour inhibition and a generalised drug hypersensitivity. Copulation activates the mesolimbic circuit increasing dopamine (DA) release in the nucleus accumbens (NAcc) and, enhanced midbrain DA neuron activity promotes endocannabinoid (eCB) release in the ventral tegmental area (VTA). The objective of this work was to explore the possible participation of DA and/or eCB transmission in the induction of these two long-lasting phenomena. To this aim we analysed the effect of blocking DA or CB1 receptors during the process of copulation to exhaustion, on the expression 24 h later, of the sexual inhibitory state and the hypersensitivity to two different drugs: 8-OH-DPAT, a 5-HT1A receptor agonist, and yohimbine, an α2-adrenoceptor antagonist. Blockade of DA receptors failed to prevent these phenomena, while blockade of CB1 receptors interfered with the appearance of the sexual inhibition and the hypersensitivity to both drugs in the sexually satiated animals. Specific blockade of CB1 receptors in the VTA during copulation to satiety mimicked these results, suggesting that both eCB-mediated effects were exerted in this brain region. It is concluded that eCBs play a role in the induction of behavioural and physiological changes, triggered by copulation to satiety, by acting at the VTA, while increased NAcc DA levels appear not to contribute to the changes induced by intense copulation. Results pose sexual satiety as a useful model for the study of brain plasticity phenomena induced by natural rewards.

    更新日期:2020-01-24
  • Effects of aging on the motor, cognitive and affective behaviors, neuroimmune responses and hippocampal gene expression
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Gaurav Singhal; Julie Morgan; Magdalene C. Jawahar; Frances Corrigan; Emily J. Jaehne; Catherine Toben; James Breen; Stephen M. Pederson; Jim Manavis; Anthony J. Hannan; Bernhard T. Baune

    The known effects of aging on the brain and behavior include impaired cognition, increases in anxiety and depressive-like behaviors, and reduced locomotor activity. Environmental exposures and interventions also influence brain functions during aging. We investigated the effects of normal aging under controlled environmental conditions and in the absence of external interventions on locomotor activity, cognition, anxiety and depressive-like behaviors, immune function and hippocampal gene expression in C57BL/6 mice. Healthy mice at 4, 9, and 14 months of age underwent behavioral testing using an established behavioral battery, followed by cellular and molecular analysis using flow cytometry, immunohistochemistry, and quantitative PCR. We found that 14-month-old mice showed significantly reduced baseline locomotion, increased anxiety, and impaired spatial memory compared to younger counterparts. However, no significant differences were observed for depressive-like behavior in the forced-swim test. Microglia numbers in the dentate gyrus, as well as CD8+ memory T cells increased towards late middle age. Aging processes exerted a significant effect on the expression of 43 genes of interest in the hippocampus. We conclude that aging is associated with specific changes in locomotor activity, cognition, anxiety-like behaviors, neuroimmune responses and hippocampal gene expression.

    更新日期:2020-01-24
  • Overinhibition mediated by parvalbumin interneurons might contribute to depression-like behavior and working memory impairment induced by lipopolysaccharide challenge
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Mu-huo Ji; Ling Zhang; Ming-jie Mao; Hui Zhang; Jiao-jiao Yang; Li-li Qiu

    Systemic inflammation induces cognitive impairments via unclear mechanisms. Accumulating evidence has demonstrated that a subset of neurons that express parvalbumin (PV) play a critical role in regulation of cognitive and emotional behavior. Thus, the aim of the present study was to test whether disruption of PV interneuron mediates systemic inflammation–induced depression-like behavior and working memory impairment by lipopolysaccharide (LPS) challenge. Here we showed that LPS induces depression-like behavior and working memory impairment, coinciding with increased PV expression, enhanced GABAergic transmission, and impaired long-term potentiation (LTP) in the hippocampus. Notably, systemic administration of NMDA (N–methyl–D–aspartate) receptor (NMDAR) antagonist ketamine was able to interfere with PV expression and reverse depression-like behavior and working memory impairment, which is probably mediated by reversing impaired LTP. In addition, flumazenil, a competitive antagonist acting at the benzodiazepine binding site of the GABAA receptor, also ameliorated these abnormal behaviors. Collectively, our study added growing evidence to the limited studies that overinhibition mediated by PV interneurons might play a critical role in LPS–induced depression-like behavior and working memory impairment.

    更新日期:2020-01-24
  • Blunted satiety in fatty Zucker rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    David P. Jarmolowicz; Tadd D. Schneider; Ale Carrillo; Jennifer L. Hudnall; Stefanie S. Stancato

    Levels of weight gain have hit an epidemic level with rates of overweight and obesity diagnoses topping all-time highs. Elevated body weight has been linked to increased rates of cardiac problems, blood pressure issues, and risk of developing type 2 diabetes. Leptin, a hormone produced by the body that is involved in energy balance by inhibiting hunger has been implicated as an underlying mechanism that differentially contributes to food-seeking motivation. Using a scientifically validated animal model of obesity, the fatty Zucker rat, which has mutated leptin receptor genes, leptin’s role in behavioral motivation can be assessed. Animals were on a 2 -h food access restriction with one-hour access to rewards in session and one hour of free-feeding access. Pre-session and post-session food access differences were evaluated in looking at motivation for food rewards during satiation while responding on differing levels of fixed-ratio schedules. The results showed robust differential behavior from satiation, demonstrating a basis for a biological mechanism involving leptin sensitivity that could underlie obesity. Although further experimentation is needed, understanding leptin could help bridge the gap in our understanding of satiation and non-satiation.

    更新日期:2020-01-24
  • Involvement of monoaminergic targets in the antidepressant- and anxiolytic-like effects of the synthetic alkamide Riparin IV: elucidation of further mechanisms through pharmacological, neurochemistry and computational approaches
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Danusio Pinheiro Sartori; Natália Ferreira de Oliveira; José Tiago Valentim; Daniel Moreira Alves da Silva; Auriana Serra Vasconcelos; Iris Cristina Maia Oliveira; Raquell de Castro Chaves; Victor Celso Cavalcanti Capibaribe; Alyne Mara Rodrigues de Carvalho; Manoela de Oliveira Rebouças; Danielle Macêdo; Adriano José Maia Chaves Filho; Marta Maria de França Fonteles; Stanley Juan Chavez Gutierrez; José Maria Barbosa-Filho; Melina Mottin; Carolina Horta Andrade; Francisca Cléa Florenço de Sousa
    更新日期:2020-01-24
  • The Medial Agranular Cortex Mediates Attentional Enhancement of Prepulse Inhibition of the Startle Reflex
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-24
    Qingxin Meng; Yu Ding; Liangjie Chen; Liang Li

    The startle reflex, which interferes with on-going cognitive/behavioral activities, is of important protective function for humans and animals. Prepulse inhibition (PPI), as an operational measure of sensorimotor gating, is the suppression of the startle reflex in response to an intense startling stimulus (pulse) when this startling stimulus is shortly preceded by a weaker non-startling stimulus (prepulse). In both humans and laboratory animals, PPI can be enhanced by facilitating selective attention to the prepulse, suggesting that higher-order cognitive/perceptual processes modulate PPI. It has been well known that both the cholinergic system located in the basal forebrain and the deep layers of the superior colliculus in the PPI-mediating circuit are top-down modulated by the medial agranular cortex (AGm), which is a subdivision of the medial prefrontal cortex (PFC) and has wide axonal connections with both cortical regions (including the posterior parietal cortex) and subcortical structures critical for attention/orientation processes. This study investigated whether the AGm is involved in attentional modulation of PPI. The results showed that PPI was enhanced by fear conditioning of the prepulse, and then further enhanced by perceived spatial separation between the conditioned prepulse and a back-ground masking noise based on the auditory precedence effect. Bilateral injection of 2-mM kynurenic acid, a broad spectrum antagonist of glutamate receptors, into the AGm, but not the primary somatosensory cortex, eliminated these two types of attentional enhancement of PPI. Thus, the AGm plays a role in facilitating attention to the prepulse and is involved in the top-down modulation of PPI.

    更新日期:2020-01-24
  • Differential Effects of Hunger on Cerebral Blood Flow in Healthy Adolescents
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-23
    Céline Charroud; Nicolas Menjot de Champfleur; Emily Sanrey; Josef Pfeuffer; Jérémy Deverdun; Emmanuelle Le Bars; Philippe Coubes

    Adolescence represents a key developmental period in terms of both mood and overweight and is linked to disturbed eating behavior. Therefore, it is essential to investigate the basis of food intake in healthy adolescents by considering mood impacts which remain largely unexplored. Hence this study aims to investigate the impact of hunger and mood on cerebral blood flow (CBF) changes in healthy adolescents. Fifteen participants underwent two MRI sessions including a 3D pseudo-continuous arterial spin labeling sequence: pre-lunch (hunger) and post-lunch (satiety). Mood was assessed using the Multiscore Depression Inventory for Children. We found higher CBF values in the posterior insula in response to hunger compared to satiety, an area of the brain which contributes to the anticipation and motivation of feeding. In response to satiation, we observed higher CBF values in the precuneus, lingual gyrus and cuneus which are involved in the aspects of response inhibition related to food intake. Furthermore, we show that correlation between mood assessment and CBF is modulated by appetite in the precuneus, anterior cingulate gyrus, anterior orbitofrontal gyrus, occipital gyrus and cuneus, suggesting that participants affected by depressed mood could use ruminative processing in order to evaluate the reward of an upcoming meal.

    更新日期:2020-01-24
  • Mirogabalin prevents repeated restraint stress-induced dysfunction in mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-23
    Takashi Iwai; Akinori Kikuchi; Misa Oyama; Shun Watanabe; Mitsuo Tanabe

    Gabapentinoids, which are the common analgesics, are also thought to be an effective treatment for anxiety disorder, which is one of several psychiatric disorders triggered and exacerbated by stress. The aim of the present study was to investigate whether mirogabalin, a recently launched gabapentinoid, protects multiple brain functions against repeated restraint stress. Adult male ddY mice were restrained for 7 days (repeated restraint stress: 2 h/day) or for 30 min (single restraint stress). Mirogabalin (intraperitoneal, intracerebroventricular or intrahippocampal injection) was administered prior to the restraint stress. Y-maze, elevated-plus maze and c-Fos immunohistochemistry were performed to evaluate learning function, anxiety levels and hippocampal neuronal activities, respectively, after the 7th day of the repeated restraint stress. Intestinal function was evaluated in terms of defecation, which was scored after the 5th day of repeated restraint stress and by the number of fecal pellets excreted after a single session of restraint stress. Repeated restraint stress induced memory dysfunction, anxiety-like behavior, an abnormal defecation score and increased hippocampal c-Fos expression. These changes were prevented by systemic administration of mirogabalin. Abnormal defecation was also induced by single restraint stress, and was inhibited by both systemic and central administration of mirogabalin, suggesting that the effect on the intestinal function was also mediated via the central nervous system. Enhancement of c-Fos expression by repeated stress was decreased by intrahippocampal injection of mirogabalin. Together, these observations suggest that mirogabalin protects multiple brain functions from repeated stress, which may be mediated by inhibition of hippocampal neuron hyperactivation.

    更新日期:2020-01-23
  • Is there a relationship between low-grade systemic inflammation and cognition in healthy people aged 60-75 years?
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-22
    M.T. Fard; L. Cribb; K. Nolidin; K. Savage; K. Wesnes; C. Stough

    Although inflammation has been associated with cognitive impairment in dementia, less is known about its role in the cognition of middle to older aged healthy people. This study utilised baseline data from the Australian Research Council Longevity Intervention (ARCLI) trial to investigate the relationship between markers of systemic inflammation (TNF-α, IL-6, IL-1β, INF-γ, IL-2, IL-4, IL-10 and hsCRP) and cognitive function in 286 healthy volunteers aged 60-75 years. We assessed cognitive functioning across domains including attention, speed of memory, working memory and episodic memory using the Cognitive Drug Research test battery. Only IFN-γ was related to cognitive function, being associated with greater odds of having low continuity of attention (log2 IFN-γ OR, 1.46; 95% CI, 1.18–1.85). The relationship between episodic memory, speed of memory and inflammation varied with BMI. In high BMI participants, increased inflammation was associated with worse cognitive function, while this association was reversed in those with low BMI. Outside of the influence of IFN-γ on attention, low-grade systemic inflammation was not robustly associated with cognitive function in this sample of middle to older aged healthy people. Further research is required to understand the role of BMI in the intersection of inflammation and cognitive function.

    更新日期:2020-01-22
  • Critical role of protein kinase G in the long-term balance between defensive and appetitive behaviors induced by aversive stimuli in Aplysia
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-22
    Ruma Chatterji; Sarah Khoury; Emanuel Salas; Marcy L. Wainwright; Riccardo Mozzachiodi

    This study investigated the signaling cascades involved in the long-term storage of the balance between defensive and appetitive behaviors observed when the mollusk Aplysia is exposed to aversive experience. In Aplysia, repeated trials of aversive stimuli induce concurrent sensitization of defensive withdrawal reflexes and suppression of feeding for at least 24 h. This long-term storage of the balance between withdrawal reflexes and feeding is sustained, at least in part, by increased excitability of the tail sensory neurons (SNs) controlling the withdrawal reflexes, and by decreased excitability of feeding decision-making neuron B51. Nitric oxide (NO) is required for the induction of both long-term sensitization and feeding suppression. At the cellular level, NO is also required for long-term decreased B51 excitability but not for long-term increased SN excitability. Here, we characterized the signaling cascade downstream of NO contributing to the long-term storage of the balance between withdrawal reflexes and feeding. We found protein kinase G (PKG) necessary for both long-term sensitization and feeding suppression, indicating that a NO-PKG cascade governs the long-term storage of the balance between defensive and appetitive responses in Aplysia. The role of PKG on feeding suppression was paralleled at the cellular level where a cGMP-PKG pathway was required for long-term decreased B51 excitability. In the defensive circuit, the cGMP-PKG pathway was not necessary for long-term increased SN excitability, suggesting that other cellular correlates of long-term sensitization might depend on the GMP-PKG cascade to sustain the behavioral change.

    更新日期:2020-01-22
  • Hippocampal overexpression of SGK1 ameliorates spatial memory, rescues Aβ pathology and actin cytoskeleton polymerization in middle-aged APP/PS1 mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-22
    Biyao Lian; Mengying liu; Zhen Lan; Tao Sun; Zhaoyou Meng; Qing Chang; Zhi Liu; Jiqiang Zhang; Chengjun Zhao

    The increasing occurrence and ineffective treatment of Alzheimer’s disease (AD) has become one of the major challenges of the world. Limited studies have shown that serum- and glucocorticoid-inducible kinase 1 (SGK1) is involved in spatial memory formation and consolidation, but its role in AD-like spatial memory impairment and the related mechanisms are not clear. In this study, we first examined the age-related changes of SGK1 in the hippocampus of female APP/PS1 (AD) mice. Based on the finding and our previous finding that significant spatial memory impairment was detected in 8-month old AD mice, SGK1-overexpressing AAV (oSGK1) was constructed and injected into the hippocampus of 9-month old AD mice. One month later, the behavior alterations, Aβ production and deposit as well as changes of CA1 spine density and selected actin polymerization remodeling proteins were examined. The results showed that significant decrease of SGK1 was detected in 10-month old AD mice. The spatial memory impairment, the production and deposit of Aβ were reversed by oSGK1. Levels of hippocampal ADAM10 (α-secretase) and IDE (Aβ degradase), actin remodeling related proteins Rictor, Rac1, Cdc42 and Profilin-1 were significantly increased after oSGK1 treatment while hippocampal BACE1 (γ-secretase) and Cofilin remained unchanged. Taken together, our findings demonstrated a pivotal role of SGK1 in the treatment of AD-related memory impairment through upregulation of non- amyloidogenic processing of APP and degradation of Aβ, increase in spine plasticity related proteins, indicating increase in hippocampal SGK1 may be a potent therapeutic target against AD.

    更新日期:2020-01-22
  • Developmental effects of daily food availability times on song behaviour and neuronal plasticity of song-control system in male zebra finches
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-21
    Ila Mishra; Twinkle Batra; Abhilash Prabhat; Neha Agarwal; Sanjay Kumar Bhardwaj; Vinod Kumar

    Food availability is a major ecological factor and affects body condition and sexual traits. Here, we investigated whether males’ song behaviour, a trait for female mate choice, was sensitive to the food availability period and its timing in songbirds. We manipulated daily food availability to 4 h in the morning or evening, with controls on food ad libitum, and assessed its effects on song behaviour and forebrain song control system in male zebra finches that were held as adult (parent) or offspring (since birth) at 24 ± 2 °C under 12 h daily photoperiod. Food restriction significantly affected both temporal and spectral features of daily song in offspring, not the parent. In offspring, we found reduced mesor (mean 24-h levels), attenuated amplitude (daily maxima relative to mesor) and altered acrophase (estimated time of daily maxima) of 24-h rhythm, and reduced motif length (in morning-fed), per motif unique syllables and an enhanced song pitch (in evening-fed). There was also a positive correlation of motif length with cheek patch and plasma testosterone levels, and of per motif syllables with cheek patch and daily activity levels in offspring. Among main song controlling forebrain nuclei, LMAN and HVC were reduced in size, and Area X and HVC showed decreased neuronal recruitment in offspring on food restrictions. These results demonstrate the importance of daily food availability and its timing in determining males’ sexual signals, and support growing evidence that among vertebrates well-fed males contain reproductive traits that females use for its mate choice.

    更新日期:2020-01-22
  • Nicotine induces resilience to chronic social defeat stress in a mouse model of water pipe tobacco exposure by activating BDNF signaling
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-21
    Mohamad Khalifeh; Rouba Hobeika; Lauretta El Hayek; Joelle Saad; Fadi Eid; Reine El-Khoury; Litsa-Maria Ghayyad; Vanessa Jabre; Patrick Nasrallah; Nour Barmo; Joseph S. Stephan; Rony Khnayzer; Christian Khalil; Sama F. Sleiman

    The purpose of this study was to investigate how nicotine in the context of water pipe tobacco smoking (WTS) affects depression and anxiety-like behaviors associated with chronic social defeat stress (CSDS). Male C57BL/6 J mice were exposed to WTS or received intraperitoneal injections of nicotine for thirty days then subjected to CSDS for ten days. During CSDS, mice were exposed to WTS or received nicotine injections. The social interaction and open-field tests were used to classify animals as resilient or susceptible to stress and to evaluate their anxiety-like behavior. After behavioral testing, mice continued to be exposed to WTS/nicotine for ten days and their behavior was reexamined. The involvement of brain derived neurotrophic factor signaling in the nicotine-mediated effects was assessed with the tropomyosin receptor kinase B (TRKB) inhibitor, ANA-12. We found that WTS promotes resilience to stress and rescues social avoidance. Even though WTS initially decreased anxiety-like behaviors, prolonged exposure after the completion of CSDS significantly induced anxiety-like behaviors. Finally, we showed that nicotine mediates the effects of WTS only on resilience to stress by increasing BDNF and TRKB levels and signaling. Our results suggest that the pathways mediating resilience to stress and anxiety are distinct and that nicotine mediates the effects of WTS on social behavior, but not anxiety, by activating BDNF signaling. Significance statement: This study reports the positive effect of WTS and nicotine on social behavior. Furthermore, it shows the negative effects of prolonged WTS on anxiety-like behaviors and suggests that these effects are not necessarily mediated by nicotine. Finally, it identifies BDNF/TRKB signaling pathway as a major mediator of the positive effects of nicotine on social interaction. As a result, this work emphasizes the importance of considering the activation status of this signaling pathway when developing smoking cessation strategies.

    更新日期:2020-01-22
  • Chronic Repeated Predatory Stress Induces Resistance to Quinine Adulteration of Ethanol in Male Mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-21
    Gladys A. Shaw; Maria Alexis M. Bent; Kimaya R. Council; A. Christian Pais; Ananda Amstadter; Jennifer T. Wolstenholme; Michael F. Miles; Gretchen N. Neigh

    Background Trauma related psychiatric disorders, such as posttraumatic stress disorder (PTSD), and alcohol use disorder (AUD) are highly comorbid illnesses that separately present an opposing, sex-specific pattern, with increased prevalence of PTSD in females and increased prevalence of AUD diagnoses in males. Likewise, PTSD is a risk factor in the development of AUD, with conflicting data on the impact of sex in the comorbid development of both disorders. Because the likelihood of experiencing more than one traumatic event is high, we aim to utilize chronic repeated predatory stress (CRPS) to query the extent to which sex interacts with CRPS to influence alcohol consumption, or cessation of consumption. Methods Male (n = 16) and female (n = 15) C57BL/6 J mice underwent CRPS or daily handling for two weeks during adolescence (P35-P49) and two weeks during adulthood (P65-P79). Following the conclusion of two rounds of repeated stress, behavior was assessed in the open field. Mice subsequently underwent a two-bottle choice intermittent ethanol access (IEA) assessment (P90-131) with the options of 20% ethanol or water. After establishing drinking behavior, increasing concentrations of quinine were added to the ethanol to assess the drinking response to adulteration of the alcohol. Results CRPS increased fecal corticosterone concentrations and anxiety-like behaviors in the open field in both male and female mice as compared to control mice that had not been exposed to CRPS. Consistent with previous reports, we observed a sex difference in alcohol consumption such that females consumed more ethanol per gram of body mass than males. In addition, CRPS reduced alcohol aversion in male mice such that higher concentrations of quinine were necessary to reduce alcohol intake as compared to control mice. CRPS did not alter alcohol-related behaviors in female mice. Conclusion Collectively, we demonstrate that repeated CRPS can induce anxiety-like behavior in both sexes but selectively influences the response to ethanol adulteration in males.

    更新日期:2020-01-22
  • Resting-state effective connectivity in the motive circuit of methamphetamine users: a case controlled fMRI study
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-21
    Meysam Siyah Mansoory; Vahid Farnia

    Methamphetamine (MA) and other psychostimulants target the motive circuit of the brain, which is involved in reward, behavioral sensitization, and relapse to drug-seeking/taking behavior. In spite of this fact, the data regarding the effective connectivity (EC) in this circuit among MA users is scarce. The present study aimed to assess resting-state EC in the motive circuit of MA users during abstinence using the fMRI technique. Seventeen MA users after abstinence and 18 normal controls were examined using a 3 T Siemens fMRI scanner. After extracting time series of the motive circuit, EC differences in the motive circuit were analyzed using dynamic causal modeling (DCM). The findings revealed that abstinent MA users had an enhanced EC from the prefrontal cortex (PFC) to the ventral palladium (VP) (PFC→VP) and on the mediodorsal thalamus (MD) self-loop (MD→MD), but they showed a decreased connectivity on the VP self-loop (VP→VP) compared to healthy controls. The findings suggest that abstinent MA users may suffer from a limited pathology in connectivity within the motive circuit involved in reward, behavioral sensitization, and relapse. The enhanced PFC→VP seems to be a compensatory mechanism to control or regulate the subcortical regions involved in reward and behavioral sensitization. Furthermore, the enhanced connectivity on the MD self-loop and the decreased connectivity on the VP self-loop in abstinent MA users may, at least partially, affect the output of the limbic system, which can be seen in the behavioral sensitization and relapse processes. Nonetheless, further investigation in this area is strongly recommended to elucidate the exact mechanisms involved.

    更新日期:2020-01-22
  • Comparing Different EEG Connectivity Methods in Young Males with ASD
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-20
    Kimaya Sarmukadam; Vicki Bitsika; Christopher F. Sharpley; Mary M.E. McMillan; Linda L. Agnew

    Although EEG connectivity data are often used to build models of the association between overt behavioural signs of Autism Spectrum Disorder (ASD) and underlying brain connectivity indices, use of a large number of possible connectivity methods across studies has produced a fairly inconsistent set of results regarding this association. To explore the level of agreement between results from five commonly-used EEG connectivity models (i.e., Coherence, Weighted Phased Lag Index- Debiased, Phase Locking Value, Phase Slope Index, Granger Causality), a sample of 41 young males with ASD provided EEG data under eyes-opened and eyes-closed conditions. There were relatively few statistically significant and/or meaningful correlations between the results obtained from the five connectivity methods, arguing for a re-estimation of the methodology used in such studies so that specific connectivity methods may be matched to particular research questions regarding the links between neural connectivity and overt behaviour within this population.

    更新日期:2020-01-21
  • A Simple Three Layer Excitatory-Inhibitory Neuronal Network for Temporal Decision-Making
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-20
    Mustafa Zeki; Fuat Balci

    Humans and animals do not only keep track of time intervals but they can also make decisions about durations. Temporal bisection is a psychophysical task that is widely used to assess the latter ability via categorization of durations as short or long. Many existing models of performance in temporal bisection primarily account for choice proportions and tend to overlook the associated response times. We propose a time-cell neural network that implements both interval timing and temporal categorization. The proposed model can keep track of time intervals based on lurching wave activity, it can learn the reference durations along with their association with different categorization responses, and finally, it can carry out the comparison of arbitrary intermediate durations to the reference durations. We compared the model's predictions about choice behavior and response times to the empirical data previously gathered from rats. We showed that this time-cell neural network can predict the canonical behavioral signatures of temporal bisection performance. Specifically, a) the proposed model can account for the sigmoidal relationship between the probability of the long choices and the test durations, b) the superimposition of choice functions on a relative time scale, c) the localization of the point of subjective equality at the geometric mean of the reference durations, and d) the differential modulation of short and long categorization response times as a function of the test durations.

    更新日期:2020-01-21
  • Circadian modulation of motivation in mice
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-17
    Julieta Acosta; Ivana L. Bussi; Macarena Esquivel; Christian Höcht; Diego A. Golombek; Patricia V. Agostino

    Most living organisms have a circadian timing system adapted to optimize the daily rhythm of exposure to the environment. This circadian system modulates several behavioral and physiological processes, including the response to natural and drug rewards. Food is the most potent natural reward across species. Food-seeking is known to be mediated by dopaminergic and serotonergic transmission in cortico-limbic pathways. In the present work, we show evidence of a circadian modulation of motivation for food reward in young (4-months old) and aged (over 1.5 years old) C57BL/6 mice. Motivation was assayed through the progressive ratio (PR) schedule. Mice under a 12:12 light/dark (LD) cycle exhibited a diurnal rhythm in motivation, becoming more motivated during the night, coincident with their active phase. This rhythm was also evident under constant dark conditions, indicating the endogenous nature of this modulation. However, circadian arrhythmicity induced by chronic exposure to constant light conditions impaired the performance in the task causing low motivation levels. Furthermore, the day/night difference in motivation was also evident even without caloric restriction when using a palatable reward. All these results were found to be unaffected by aging. Taken together, our results indicate that motivation for food reward is regulated in a circadian manner, independent of the nutritional status and the nature of the reward, and that this rhythmic modulation is not affected by aging. These results may contribute to improve treatment related to psychiatric disorders or drugs of abuse, taking into account potential mechanisms of circadian modulation of motivational states.

    更新日期:2020-01-17
  • Effect of Brightness of Visual Stimuli on EEG Signals
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-17
    Kübra Eroğlu; Temel Kayıkçıoğlu; Onur Osman

    The aim of this study was to examine brightness effect, which is the perceptual property of visual stimuli, on brain responses obtained during visual processing of these stimuli. For this purpose, brain responses of the brain to changes in brightness were explored comparatively using different emotional images (pleasant, unpleasant and neutral) with different luminance levels. In the study, electroencephalography recordings from 12 different electrode sites of 31 healthy participants were used. The power spectra obtained from the analysis of the recordings using short time Fourier transform were analyzed, and a statistical analysis was performed on features extracted from these power spectra. Statistical findings were compared with those obtained from behavioral data. The results showed that the brightness of visual stimuli affected the power of brain responses depending on frequency, time and location. According to the statistically verified findings, the increase in the brightness of pleasant and neutral images increased the average power of responses in the parietal and occipital regions whereas the increase in the brightness of unpleasant images decreased the average power of responses in these regions. Moreover, the statistical results obtained for unpleasant images were found to be in accordance with the behavioral data. The results revealed that the brightness of visual stimuli could be represented by changing the activity power of the brain cortex. The findings emphasized that the brightness of visual stimuli should be viewed as an important parameter in studies using emotional image techniques such as image classification, emotion evaluation and neuro-marketing.

    更新日期:2020-01-17
  • Transcranial direct current stimulation improves risky decision making in women but not in men: a sham-controlled study
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-17
    J.J. León; A. Sánchez-Kuhn; P. Fernández-Martín; M.A. Páez-Pérez; C. Thomas; A. Datta; F. Sánchez-Santed; P Flores

    Behavioral and anatomical sex-related differences have been traditionally found in decision-making processes assessed by Iowa Gambling Task (IGT). So far, the administration of transcranial direct current stimulation (tDCS) over orbitofrontal regions has shown an enhancing effect over decision-making. However, it is unknown whether there is a sex-dependent effect of stimulation in decision-making, a key question considering previous differences between men and women in IGT and the influence of individual differences in tDCS. The present study examines, at first time, the interaction between sex and tDCS in decision-making. For that aim, in a first experimental phase, ninety-two healthy participants performed the IGT. In a second phase, sixty-one participants received 20 min of anodal or sham tDCS over the right orbitofrontal cortex (rOFC) in a single-session pre-post sham-controlled study. To support the focality of the montage, a Stop Signal Task (SST) was used as a control task and also a numerical simulation of current flow distribution was performed. According to literature, in the first phase, results showed that men outperformed women in the IGT. In the second phase, the stimulation varied the IGT performance according to a sex specific manner: anodal tDCS increased the IGT performance in women, while in men; the stimulation did not produce any effect. Results were mediated by sex-specific morphological differences. These results highlight the necessity to consider the interaction of sex with the effect of the stimulation in future tDCS protocols, specifically in future clinical studies.

    更新日期:2020-01-17
  • The effect of erythropoietin on electroconvulsive stimulation induced cognitive impairment in rats
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-16
    Kristian Kjær; Martin Balslev Jørgensen; Ida Hageman; Kamilla Woznica Miskowiak; Gitta Wörtwein

    Electroconvulsive therapy (ECT) is the most effective and fast-acting treatment for severe depression but associated with troublesome cognitive side-effects. Systemically administered erythropoietin (EPO) crosses the blood-brain-barrier and is a promising treatment for cognitive dysfunction in a wide array of neuropsychiatric and neurological disorders. In this study we trained rats to locate a submerged platform in a water maze and then subjected them to electroconvulsive stimulations (ECS, the rodent equivalent to ECT) and EPO treatment. We then analysed their ability to remember and relearn the location of the platform. In addition, we examined “wall-clinging” (thigmotaxis), a behavioural indicator of stress. ECS caused significant deficit in a probe trial administered after three weeks (nine stimulations) as well as one week (six stimulations) of treatment, indicative of induction of retrograde amnesia. ECS had no effect on relearning of the water maze task or performance in a subsequent probe trial. EPO treatment did not ameliorate the ECS-induced retrograde amnesia, but after nine ECS stimulations the animals that had received EPO relearned the position of the hidden platform faster than the animals that had not. We also found EPO to decrease “wall-clinging” behaviour, suggesting an effect of EPO on the stress response in rats. Thus, we establish the Morris Water Maze as a suitable model for ECS-induced memory loss in rats and provide some evidence for potential beneficial effects of EPO.

    更新日期:2020-01-16
  • Aberrant resting-state interhemispheric functional connectivity in patients with postpartum depression
    Behav. Brain Res. (IF 2.770) Pub Date : 2020-01-16
    Shufen Zhang; Wei Wang; Gang Wang; Bo Li; Liping Chai; Jianping Guo; Xin Gao

    The aim of this study is to investigate the alterations of interhemispheric functional connectivity in patients with postpartum depression (PPD) during resting state, and their potential correlations with clinical severity. Twenty- eight patients with PPD and twenty-five matched healthy postpartum (HP) women within 4 weeks after delivery were recruited and performed resting-state functional magnetic resonance imaging(fMRI) scans. Voxel-mirrored homotopic connectivity (VMHC), which is useful for exploring interhemispheric functional connectivity, and has been widely utilized to identify abnormal functional connectivity between the symmetrical brain regions in many diseases, was calculated in the present study, and intergroup VMHC differences in the voxel manner were analyzed. Correlations between VMHC values and clinical variables were also analyzed. Compared with HP, patients with PPD exhibited significantly decreased VMHC values in bilateral dorsomedial prefrontal cortex (dmPFC), dorsal anterior cingulate cortex (dACC) and orbitofrontal cortex (OFC). Furthermore, VMHC values within the dmPFC negatively correlated with the Edinburgh postpartum depression scale (EPDS) score. These findings suggested that functional coordination between several homotopic brain regions were impaired in patients with PPD. This study provided evidences of aberrant interhemispheric connectivity within brain regions involved in the maternal care network in PPD, and may contribute to the further understanding of the neural mechanism underlying PPD.

    更新日期:2020-01-16
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