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  • Activation of Different Heterodimers of TLR2 Distinctly Mediates Pain and Itch
    Neuroscience (IF 3.244) Pub Date : 2020-01-16
    Ting-Ting Wang; Xian-Yun Xu; Wei Lin; Dan-Dan Hu; Wu Shi; Xin-Jia; Hui Wang; Ning-Jing Song; Yu-Qiu Zhang; Ling Zhang

    Toll-like receptors (TLRs) have been implicated in pain and itch regulation. TLR2, a TLR family member that detects microbial membrane components, has been implicated in pathologic pain. However, the role of TLR2 in pruritic and nociceptive responses has not been thoroughly investigated. In this study, we found that TLR2 was expressed in mouse dorsal root ganglia (DRG) and trigeminal ganglia (TG) neurons. Itch and pain behaviors, including histamine-dependent and histamine-independent acute itching, acetone/diethyl ether/water and 2,4-dinitrofluorobenzene-induced chronic itching and inflammatory pain, were largely attenuated in TLR2 knockout (KO) mice. The TLR2 agonist Pam3CSK4, which targets TLR2/1 heterodimers, evoked pain and itch behavior, whereas lipoteichoic acid (LTA) and zymosan, which recognize TLR2/6 heterodimers, produced only pain response. The TLR2 agonist-induced nociceptive and pruritic behaviors were largely diminished in transient receptor potential vanilloid 1 (TRPV1) and transient receptor potential ankyrin 1 (TRPA1) KO mice. Finally, Pam3Csk4 and zymosan increased the [Ca2+]i in DRG neurons from wild-type mice. However, the enhancement of [Ca2+]i was largely inhibited in the DRG neurons from TRPV1 and TRPA1 KO mice. Our results demonstrate that TLR2 is involved in different itch and pain behaviors through activating TLR1/TLR2 or TLR6/TLR2 heterodimers via TRPV1 and TRPA1 channels.

    更新日期:2020-01-17
  • Overexpression of microRNA-9a-5p ameliorates NLRP1 inflammasome-mediated ischemic injury in rats following ischemic stroke
    Neuroscience (IF 3.244) Pub Date : 2020-01-16
    Cao yuze; Zhang huixue; Lu xiaoyu; Wang Jianjian; Zhang xiaoming; Sun shengnan; Bao zhonglei; Tian wenqi; Ning shangwei; Wang lihua; Cui liying
    更新日期:2020-01-17
  • The differential effect of treadmill exercise intensity on hippocampal soluble aβ and lipid metabolism in APP/PS1 mice
    Neuroscience (IF 3.244) Pub Date : 2020-01-16
    B. Zeng; G. Zhao; H.L. Liu

    Alzheimer's disease (AD) is characterized clinically by progressive impairments in learning and memory. Accumulating evidence suggests that regular exercise plays a neuroprotective role in aging-associated memory loss. Our previous study has confirmed that long-term treadmill exercise initiated either before or during the onset of β-amyloid (Aβ) pathology, was beneficial for reducing the levels of soluble Aβ and further improved cognition. In this study, in APP/PS1 mice, we assessed changes in soluble Aβ, and various blood biochemistry and molecular biological indices to assess whether exercise modulated lipid metabolism and thereby decelerated AD progression. Our results show that long-term treadmill exercise reduced the total cholesterol, triglyceride, and low-density lipoprotein cholesterol levels, and increased the level of high-density lipoprotein cholesterol. Exercise also decreased the levels of soluble Aβ1-40 and Aβ1-42, down-regulated retinoid X receptor expression, and up-regulated liver X receptor, Apolipoprotein E, Low density lipoprotein receptor, Low density lipoprotein receptor-related protein 1, and ATP-binding cassette transporter A1 expression. This indicates that long-term treadmill exercise alters the lipoprotein content, increases lipid metabolism and cholesterol transportation, reduces the soluble Aβ, and therein plays an important neuroprotective role and delays AD progression. We further show that medium exercise intensity (60%-70% of maximal oxygen uptake) was more efficacious in increasing lipid metabolism and reducing blood lipid levels and soluble Aβ levels, than low-intensity exercise (45-55% of maximal oxygen uptake). This research has broad prospects and implications, and offers a theoretical basis for the prevention of AD.

    更新日期:2020-01-17
  • Inhibition of 5 α reductase impairs cognitive performance, alters dendritic morphology and increases tau phosphorylation in the hippocampus of male 3xTg-AD mice
    Neuroscience (IF 3.244) Pub Date : 2020-01-16
    Ari Loren Mendell; Samantha D. Creighton; Hayley A. Wilson; Kristen H. Jardine; Lauren Isaacs; Boyer D. Winters; Neil J. MacLusky

    Recent work has suggested that 5α-reduced metabolites of testosterone may contribute to the neuroprotection conferred by their parent androgen, as well as to sex differences in the incidence and progression of Alzheimer’s disease (AD). This study investigated the effects of inhibiting 5α-reductase on object recognition memory (ORM), hippocampal dendritic morphology and proteins involved in AD pathology, in male 3xTg-AD mice. Male 6-month old wild-type or 3xTg-AD mice received daily injections of finasteride (50 mg/kg i.p.) or vehicle (18% β-cyclodextrin, 1% v/b.w.) for 20 days. Female wild-type and 3xTg-AD mice received only the vehicle. Finasteride treatment differentially impaired ORM in males after short-term (3xTg-AD only) or long-term (3xTg-AD and wild-type) retention delays. Dendritic spine density and dendritic branching of pyramidal neurons in the CA3 hippocampal subfield were significantly lower in 3xTg-AD females than in males. Finasteride reduced CA3 dendritic branching and spine density in 3xTg-AD males, to within the range observed in vehicle-treated females. In the CA1 hippocampal subfield, dendritic branching and spine density were reduced in both male and female 3xTg-AD mice, compared to wild type controls. Hippocampal amyloid β levels were substantially higher in 3xTg–AD females compared to both vehicle and finasteride-treated 3xTg–AD males. Site-specific Tau phosphorylation was higher in 3xTg-AD mice compared to sex-matched wild-type controls, increasing slightly after finasteride treatment. These results suggest that 5α-reduced neurosteroids may play a role in testosterone-mediated neuroprotection and may contribute to sex differences in the development and severity of AD.

    更新日期:2020-01-17
  • Mixed effecs of low-dose ethanol on cortical and hippocampal theta oscillations
    Neuroscience (IF 3.244) Pub Date : 2020-01-16
    Calvin K. Young; Neil McNaughton

    Ethanol is one of the most widely used drugs – with many psychoactive effects, including anxiolysis. The deleterious effects on brain function and general health of chronic and high-level ethanol use are well-studied. However, the neurophysiology of acute low dose ethanol has not been systematically investigated. Here, we examined the effects of low dose (0.25 and 0.5 g/kg) ethanol on midline (prefrontal, cingulate and retrosplenial) neocortical and hippocampal theta oscillations in freely moving rats. We also tested low dose ethanol on reticular-elicited and running-elicited hippocampal theta frequency and assessed the linear relationship of theta frequency to stimulation intensity and running speed, respectively. Low dose ethanol had mixed effects on neocortical theta oscillations. It most reliably reduced theta frequency, produced a weak inverted-U effect on theta power, and had no detectable effect on cortico-hippocampal theta coherence. Ethanol dose-dependently decreased the y-intercept of the speed-theta frequency function without affecting the slope, but decreased the slope of the stimulation intensity-theta frequency function without affecting the y-intercept; thus decreasing theta frequency in both cases. We conclude low dose ethanol has weak but detectable effects on neocortical and hippocampal theta oscillations. These effects may underlie positive cognitive and behavioural outcomes reported in the literature using low dose ethanol. The double dissociation of slope and y-intercept specific changes relating to different methods of hippocampal theta elicitation presents the potential to probe multiple mechanisms contributing to anxiolytic effects on theta and so hippocampal function.

    更新日期:2020-01-17
  • A low cost antibody signal enhancer improves immunolabeling in cell culture, primate brain and human cancer biopsy
    Neuroscience (IF 3.244) Pub Date : 2020-01-16
    Catalina Flores-Maldonado; M. Estela Albino-Sánchez; Juan D. Rodríguez-Callejas; Argel Estrada-Mondragon; Ismael León-Galicia; Raúl Maqueda-Alfaro; Claudia Perez-Cruz; Eberhard Fuchs; Alejandro García-Carrancá; Rubén G. Contreras; Fanis Missirlis; Abraham Rosas-Arellano

    The use of antibodies to identify neuronal receptors, neurotransmitters, cytoskeletal elements or pathologic protein aggregates, ion channels, adhesion molecules or other cell-type specific markers, is common practice in neuroscience. Antibody detection systems are often based on confocal, epifluorescence or brightfield microscopy. Three types of technical issues can interfere with immunolabeling: low abundance of the target protein, low specific affinity of the antibody and/or signal background sometimes related to tissue fixation. Here, giving tribute to Professor Miledi’s mentorship, we propose the application of an antibody signal enhancer (ASE) solution based on glycine, hydrogen peroxide and a detergent mix as a simple, low cost, protocol variation that significantly and specifically improves the signal to noise ratio during immunostaining experiments. We describe three new settings in which ASE improves the detection of a variety of antibodies applied on long-time stored non-human primate brain sections, cell culture monolayers and on squamous carcinomas retrieved from cervical cancer patients. The significant improvement of ASE over optimized immunohistochemical protocols used in clinical practice (i.e. cancer detection) combined with its simplicity and low cost makes it an attractive method for biomedical applications.

    更新日期:2020-01-17
  • Acute exercise modulates pain-induced response on sensorimotor cortex ∼20 Hz oscillation
    Neuroscience (IF 3.244) Pub Date : 2020-01-11
    Pekka Hautasaari; Susanna McLellan; Maija Koskio; Heidi Pesonen; Ina M. Tarkka

    Exercise affects positively on self-reported pain in musculoskeletal pain conditions possibly via top-down pain inhibitory networks. However, the role of cortical activity in these networks is unclear. The aim of the current exploratory study was to investigate the effects of acute exercise on cortical nociceptive processing and specifically the excitability in the human sensorimotor cortex. Five healthy adults (mean age 32.8 years) were recorded with a whole-head 306-channel magnetoencephalography (MEG, Elekta Neuromag® Triux™). Participant’s right hand third fingertip was stimulated electrically with an intracutaneous non-magnetic copper tip electrode before and immediately after an exercise task. Stimulus intensity was set individually so that the stimulation was subjectively rated as moderately painful, 6-7 on a visual analog scale. The acute exercise task was an isometric three-minute fatiguing left hand contraction with force-level at 30% of maximum voluntary contraction. Data analysis was conducted as event-related evoked field and frequency analysis. Early cortical activations after stimulation were localized in the primary and secondary somatosensory cortices. The main result demonstrated modulation of cortical nociceptive processing in the sensorimotor cortex ∼20 Hz rhythm immediately after the acute exercise. In conclusion, acute exercise may have an effect on nociceptive processing in the sensorimotor cortex on oscillatory level. Research on cortical oscillations analyzing interaction between nociception and exercise is limited. This study presents results indicating brain oscillatory activity as a feasible research target for examining mechanisms interacting between exercise and cortical nociceptive processing.

    更新日期:2020-01-13
  • Tolerance induced by DHPG postconditioning is mediated by the PI3K/Akt/GSK3β signalling pathway in an in vitro model of cerebral ischemia
    Neuroscience (IF 3.244) Pub Date : 2020-01-11
    Elisabetta Gerace; Tania Scartabelli; Domenico E Pellegrini-Giampietro; Elisa Landucci
    更新日期:2020-01-13
  • 更新日期:2020-01-13
  • Bulleyaconitine A inhibits itch and itch sensitization induced by histamine and chloroquine
    Neuroscience (IF 3.244) Pub Date : 2020-01-11
    Zhuo Huang; Xin Zhou; Jun Zhang; Chun-Lin Mai; Jie-Zhen Mai; Chong Liu; Hui Zhang; Xian-Guo Liu
    更新日期:2020-01-13
  • Repeated Moderate Sound Exposure Causes Accumulated Trauma to Cochlear Ribbon Synapses in Mice
    Neuroscience (IF 3.244) Pub Date : 2020-01-11
    Yangtuo Luo; Tengfei Qu; Qingling Song; Yue Qi; Shukui Yu; Shusheng Gong; Ke Liu; Xuejun Jiang

    Repeated induction of a temporary threshold shift (TTS) may result in a permanent threshold shift (PTS) and is thought to be associated with early onset of age-related hearing loss (ARHL). The possibility that a PTS might be induced by administration of repeated TTS-inducing noise exposures (NEs) over a short period during early adulthood has not been formally investigated. We aimed to investigate possible cumulative acoustic overstimulation effects that permanently shift the auditory threshold. Young adult C57BL/6J mice were exposed twice to moderate white noise in an experimental design that minimized the effects of aging. The first exposure resulted in a reversible noise-induced hearing loss (NIHL) measured as recoverable alterations in auditory brainstem response (ABR) thresholds, waveform amplitudes, and numbers of ribbon synapses. The second NE with the same parameters caused persistent threshold shifts, wave I amplitude reductions, wave IV/I ratio enhancements, and synaptic losses, even though recovery time sufficient for a TTS had been provided. The pattern of PTS resembled NIHL since the observed impairments tonotopically followed the power spectrum of the noise insult, rather than ARHL, which distributes at higher frequencies. No significant changes were observed in the control group as the mice aged. To conclude, our results demonstrate a cumulative effect of repetitive TTS-inducing NE on hearing function and synaptic plasticity that does not cause premature ARHL, thereby providing insight into the pathophysiological mechanisms underlying NIHL and ARHL.

    更新日期:2020-01-13
  • Neural signatures of working memory in age-related hearing loss
    Neuroscience (IF 3.244) Pub Date : 2020-01-11
    Stephanie Rosemann; Christiane M. Thiel

    Age-related hearing loss affects the ability to hear high frequencies and therefore leads to difficulties in understanding speech, particularly under adverse listening conditions. This decrease in hearing can be partly compensated by the recruitment of executive functions, such as working memory. The compensatory effort may, however, lead to a decrease in available neural resources compromising cognitive abilities. We here aim to investigate whether mild to moderate hearing loss impacts prefrontal functions and related executive processes and whether these are related to speech-in-noise perception abilities. Nineteen hard of hearing and nineteen age-matched normal-hearing participants performed a working memory task to drive prefrontal activity, which was gauged with functional magnetic resonance imaging. In addition, speech-in-noise understanding, cognitive flexibility and inhibition control were assessed. Our results showed no differences in frontoparietal activation patterns and working memory performance between normal-hearing and hard of hearing participants. The behavioral assessment of further executive functions, however, provided evidence of lower cognitive flexibility in hard of hearing participants. Cognitive flexibility and hearing abilities further predicted speech-in-noise perception. We conclude that neural and behavioral signatures of working memory are intact in mild to moderate hearing loss. Moreover, cognitive flexibility seems to be closely related to hearing impairment and speech-in-noise perception and should, therefore, be investigated in future studies assessing age-related hearing loss and its implications on prefrontal functions.

    更新日期:2020-01-13
  • Ubiquitination and E3 Ubiquitin Ligases in Rare Neurological Diseases with Comorbid Epilepsy
    Neuroscience (IF 3.244) Pub Date : 2020-01-10
    Jiuhe Zhu; Nien-Pei Tsai

    Ubiquitination is a post-translational modification that can dynamically alter the function, degradation and transport of a protein, as well as its interaction with other proteins, and activity of an enzyme. Dysfunctional ubiquitination is detrimental to normal cellular functions, and can result in severe diseases. Over the last decade, although much research has focused on deciphering the role of the ubiquitination/ubiquitin proteasome system in the onset and progression of various neurological disorders, the specific relationship between ubiquitination and various epilepsies has not been carefully reviewed. As an increasing amount of research has revealed the roles of ubiquitination in the trafficking of ion channels and the turn-over of synaptic receptors, it is crucial to take a deeper look into ubiquitination-associated epilepsy. Here, we review the role of ubiquitination in maintaining normal cellular activities in neurons and recent findings on the dysregulation of ubiquitination in epilepsy. We particularly focus on rare neurological disorders with comorbid epilepsy in the hope of drawing more attention to this area. Through categorizing epilepsy-associated E3 ubiquitin ligases and their substrates and discussing ubiquitination-related rare neurological disorders, we summarize where the field stands at the moment and what directions we should consider in the future.

    更新日期:2020-01-11
  • Prolactin, Estradiol and Testosterone Differentially Impact Human Hippocampal Neurogenesis in an In Vitro Model
    Neuroscience (IF 3.244) Pub Date : 2020-01-10
    Demelza M. Smeeth; Ioanna Kourouzidou; Rodrigo R.R. Duarte; Timothy R. Powell; Sandrine Thuret

    Previous studies have indicated that sex hormones such as prolactin, estradiol and testosterone may play a role in the modulation of adult hippocampal neurogenesis (AHN) in rodents and non-human primates, but so far there has been no investigation of their impact on human hippocampal neurogenesis. Here, we quantify the expression levels of the relevant receptors in human post-mortem hippocampal tissue and a human hippocampal progenitor cell (HPC) line. Secondly, we investigate how these hormones modulate hippocampal neurogenesis using a human in vitro cellular model. Human female HPCs were cultured with biologically relevant concentrations of either prolactin, estradiol or testosterone. Bromodeoxyuridine (BrdU) incorporation, immunocytochemistry (ICC) and high-throughput analyses were used to quantify markers determining cell fate after HPCs were either maintained in a proliferative state or allowed to differentiate in the presence of these hormones. In proliferating cells, estrogen and testosterone increased cell density but had no clear effect on markers of proliferation or cell death to account for this. In differentiating cells, a 3-day treatment of prolactin elicited a transient effect, whereby it increased the proportion of microtubule-associated protein 2 (MAP2)-positive and Doublecortin (DCX)-positive cells, but this effect was not apparent after 7-days. At this timepoint we instead observe a decrease in proliferation. Overall, our study demonstrates relatively minor, and possibly short-term effects of sex hormones on hippocampal neurogenesis in human cells. Further work will be needed to understand if our results differ to previous animal research due to species-specific differences, or whether it relates to limitations of our in vitro model.

    更新日期:2020-01-11
  • High Behavioral Sensitivity to Carbon Dioxide Associates with Enhanced Fear Memory and Altered Forebrain Neuronal Activation
    Neuroscience (IF 3.244) Pub Date : 2020-01-10
    Katherine M.J. McMurray; Alijah Gray; Paul Horn; Renu Sah

    There is considerable interest in pre-trauma individual differences that may contribute to increased risk for developing post-traumatic stress disorder (PTSD). Identification of underlying vulnerability factors that predict differential responses to traumatic experiences is important. Recently, the relevance of homeostatic perturbations in shaping long-term behavior has been recognized. Sensitivity to CO2 inhalation, a homeostatic threat to survival, was shown to associate with the later development of PTSD symptoms in veterans. Here, we investigated whether behavioral sensitivity to CO2 associates with PTSD-relevant behaviors and alters forebrain fear circuitry in mice. Mice were exposed to 5% CO2 or air inhalation and tested one week later on acoustic startle and footshock contextual fear conditioning, extinction and reinstatement. CO2 inhalation evoked heterogenous freezing behaviors (high freezing CO2-H and low freezing CO2-L) that significantly associated with fear conditioning and extinction behaviors. CO2-H mice elicited potentiated conditioned fear and delayed extinction while behavioral responses in CO2-L mice were similar to the air group. Persistent neuronal activation marker ΔFosB immunostaining revealed altered regional neuronal activation within the hippocampus, amygdala and medial pre-frontal cortex that correlated with conditioned fear and extinction. Inter-regional co-activation mapping revealed disruptions in the coordinated activity of hippocampal dentate-amygdala-infralimbic regions and infralimbic-prelimbic associations in CO2-H mice that may explain their enhanced fear phenotype. In conclusion, our data support an association of behavioral sensitivity to interoceptive threats such as CO2 with altered fear responding to exteroceptive threats and suggest that “CO2-sensitive” individuals may be susceptible to developing PTSD.

    更新日期:2020-01-11
  • Cross-species analyses of intra-species behavioral differences in mammals and fish
    Neuroscience (IF 3.244) Pub Date : 2020-01-10
    Konstantin A. Demin; Anton M. Lakstygal; Andrey D. Volgin; Murilo S. de Abreu; Rafael Genario; Erik T. Alpyshov; Nazar Serikuly; Dongmei Wang; Jiantao Wang; Dongni Yan; Mengyao Wang; LongEn Yang; Guojun Hu; Maksim Bytov; Konstantin A. Zabegalov; Aleksander Zhdanov; Brian H. Harvey; Fabiano Costa; Allan V. Kalueff

    Multiple species display robust behavioral variance among individuals due to genetic, genomic, epigenetic, neuroplasticity and environmental factors. Behavioral individuality has been extensively studied in various animal models, including rodents and other mammals. Recently, fish, such zebrafish (Danio rerio), have emerged as powerful aquatic model organisms with overt individual differences in behavioral, nociceptive and other CNS traits. Here, we evaluate individual behavioral differences in mammals and fish, emphasizing the importance of cross-species analyses of intraspecies variance in experimental models of normal and pathological CNS functions.

    更新日期:2020-01-11
  • Therapeutic and preventive effect of voluntary running wheel exercise on social defeat stress (SDS)-induced depressive-like behavior and chronic pain in mice
    Neuroscience (IF 3.244) Pub Date : 2020-01-09
    M. Pagliusi; I.J.M. Bonet; A.F. Brandão; S.F. Magalhães; C.H. Tambeli; C.A. Parada; C.R. Sartori

    Major depressive disorders (MDD) and chronic pain (CP) affect significant portion of the world's population and have high comorbidity rate. Social defeat stress (SDS) model was standardized in mice and can trigger depressive-like behavior and chronic pain. Based especially on clinical trials showing an effective preventive and therapeutic effect of physical exercise on CP and symptoms associated with MDD, this study aimed to investigate if the voluntary running wheel exercise can exert these effects in mice submitted to the 10-day SDS protocol, using fluoxetine as positive control. For this, we ran two set of experiments: in the first set mice started performing voluntary running wheel exercise after submitted to SDS and, in the second set, mice performed voluntary running wheel exercise before and during SDS. Mechanical and chemical hyperalgesia was analyzed through electronic von Frey and capsaicin test, respectively. Depressive-like behavior was assessed through social interaction test. Our results showed that the voluntary running wheel exercise was more effective than fluoxetine reversing the SDS-induced persistent hyperalgesia and both, fluoxetine and voluntary running wheel exercise, was effective reversing SDS-induced social avoidance. Also, voluntary running wheel exercise is an effective tool preventing both hyperalgesia and social avoidance induced by SDS. To the best of our knowledge, this was the first study using physical exercise as a therapeutic and preventive tool for chronic pain and depressive-like behavior simultaneously induced by social stress.

    更新日期:2020-01-09
  • Differential modulation of motor unit properties from the separate components of the triceps surae in humans
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Kalter Hali; Brian H Dalton; Brad Harwood; Andrew F Fessler; Geoffrey A Power; Charles L Rice

    The triceps surae is comprised of the soleus, and medial (MG) and lateral (LG) gastrocnemii. Modulation of triceps surae motor units (MUs) is context- and muscle-dependent, yet it is unknown how the disparate components of the triceps surae work together to achieve the common goal of high-intensity voluntary isometric plantar flexion torque gradation. Thus, the purpose was to assess the interrelationships between MU recruitment thresholds (MURTs) and MU discharge rates (MUDRs) among these three muscles during contractions from low to high intensities. We sampled 157 MU action potential trains from the MG (68), LG (38) and soleus (51) using fine-wire intramuscular electromyography during voluntary ramp isometric contractions up to 100% maximal voluntary contraction. The soleus exhibited 41 and 54% lower MURTs compared to the MG (p < 0.0001) and LG (p < 0.0001), respectively, whereas MG MURTs were 22% lower than the LG (p < 0.0001). Initial MUDRs were 35 and 26% greater for the LG compared with the MG (p < 0.0001) and soleus (p < 0.0001), but no difference was detected between the MG and soleus (p = 0.28). Finally, initial MUDRs displayed a positive relationship with MURTs for each independent triceps surae component (p ≤ 0.002). The relative differences in MU properties of each muscle in this synergistic group illustrate that MU control strategies are likely optimized with respect to the relative contribution of each muscle to plantar flexion torque or functional roles.

    更新日期:2020-01-07
  • Tuning of standing postural responses to instability and cost function
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Matteo Bertucco; Amber Dunning; Terence D. Sanger

    Whole-body movements are performed daily, and humans must constantly take into account the inherent instability of a standing posture. At times these movements may be performed in risky environments and when facing different costs of failure. The aim of the study was to test the hypothesis that in upright stance participants continuously estimate both probability of failure and cost of failure such that their postural responses will be based on these estimates. We designed a snowboard riding simulation experiment where participants were asked to control the position of a moving snowboard within a snow track in a risky environment. Cost functions were provided by modifying the penalty of riding in the area adjacent to the snow track. Uncertainty was modified by changing the gain of postural responses while participants were standing on a rocker board. We demonstrated that participants continually evaluated the environmental cost function and compensated for additional risk with feedback-based postural changes, even when probability of failure was negligible. Results showed also that the participants’ estimates of the probability of failure accounted for their own inherent instability. Moreover, participants showed a tendency to overweight large probabilities of failure with more biomechanically constrained standing postures that results in suboptimal estimates of risky environments. Overall, our results suggest that participants tune their standing postural responses by empirically estimating the cost of failure and the uncertainty level in order to minimize the risk of falling when cost is high.

    更新日期:2020-01-07
  • Glycosphingolipid biosynthesis pathway in the spinal cord and dorsal root ganglia during inflammatory pain: early and late changes in expression patterns of glycosyltransferase genes
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Motoki Morita; Shun Watanabe; Misa Oyama; Takashi Iwai; Mitsuo Tanabe

    Glycosphingolipids (GSLs) are abundant, ceramide-containing lipids in the nervous system that play key functional roles in pain and inflammation. We measured gene expression (Ugcg, St3gal5, St8sia1, B4galNT1, Ugt8a, and Gal3st1) of glycosyltransferases involved in GSL synthesis in murine dorsal root ganglion (DRG) and spinal cord after complete Freund’s adjuvant (CFA)-induced unilateral hind-paw inflammation (1 day vs. 15 days). Chronic inflammation (15 days) sensitized both ipsilateral and contralateral paws to pain. One day of induced unilateral hind-paw inflammation (1d-IUHI) increased Ugcg, St8sia1, B4galnt1, and Gal3st1 expression in ipsilateral cord, suggesting that sulfatide and b-series gangliosides were also elevated. In addition, 1d-IUHI increased Ugcg, st3gal5 and B4galnt1 expression in contralateral cord, suggesting that sulfatide and a-/b-series gangliosides were elevated. By contrast, 1d-IUHI decreased Ugcg, St3gal5, and St8sia1 expression bilaterally in the DRG, suggesting that b-series gangliosides were depressed. Since intrathecal injection of b-series ganglioside induced mechanical allodynia in naïve mice, it seems reasonable that b-series gangliosides synthesized from upregulated St8sia1 in the ipsilateral spinal cord are involved in mechanical allodynia. By contrast, chronic inflammation led to a decrease of Ugcg, St3gal5, B4galnt1, and Gal3st1 expression in spinal cord bilaterally and an increase of St8sia1 expression in the ipsilateral DRG, suggesting that a-/b-series gangliosides in the spinal cord decreased and b-series gangliosides in ipsilateral DRG increased. These changes in glycosyltransferase gene expression in the DRG and the spinal cord may contribute to the modification of pain sensitivity in both inflamed and non-inflamed tissues and the transition from early to chronic inflammatory pain.

    更新日期:2020-01-07
  • Differential effects of short-term environmental enrichment in juvenile and adult mice
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Kathleen Chandler; Hosnia Dosso; Stephanie Simard; Sara Siddiqi; Chris Rudyk; Natalina Salmaso

    Environmental enrichment has been shown to increase cognitive abilities and accelerate recovery from a number of disease states. Typically, enrichment protocols last from four to eight weeks, however, it has previously been shown that two weeks of environmental enrichment is sufficient to increase cognitive abilities and the proliferation of the astroglial stem cell pool in juvenile mice. The current study examines whether a short-term enrichment protocol can induce similar effects in adults as compared to juveniles. Using juvenile and adult wild-type mice, we examined the effects of short-term environmental enrichment (including a running wheel) on cognitive abilities, anxiety-like behaviour, and the stem cell potential of sub- ventricular neural stem cells (NSC’s) in vitro using neurosphere assays. We found that short-term environmental enrichment decreased anxiety behaviour and increased overall memory abilities similarly in juveniles and adults. However, the rate of acquisition on the Morris water maze, hippocampal Sox2 and Ki67 expression, and neurosphere potential increased in response to enrichment only in juveniles, suggesting that the effects of enrichment on these measures are age dependant. Together, these data suggest that the potential beneficial effects of environmental manipulations decrease with age.

    更新日期:2020-01-07
  • Repetitive transcranial magnetic stimulation elicits antidepressant- and anxiolytic- like effect via nuclear factor-E2-related factor 2-mediated anti-inflammation mechanism in rats
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Li Tian; Sisi Sun; Longbiao Cui; Shiquan Wang; Zhengwu Peng; Qingrong Tan; Wugang Hou; Min Cai

    Repetitive transcranial magnetic stimulation (rTMS) treatment is widely accepted as an evidence-based treatment option for depression and anxiety. However, the underlying mechanism of this treatment maneuver has not been clearly understood. The chronic unpredictable mild stress (CUMS) procedure was used to establish depression and anxiety-like behavior in rats. The rTMS was performed with a commercially available stimulator for seven consecutive days, and then depression and anxiety-like behaviors were subsequently measured. The expression of nuclear factor-E2-related factor 2 (Nrf2) was measured by western-blot, and the level of tumor necrosis factor-α (TNF-α), inducible nitric oxide synthase (iNOS), interleukin-1β (IL-1β), and interleukin-6 (IL-6) was measured with ELISA analyzing kits. Furthermore, a small interfering RNA was employed to knockdown Nrf2, after which the neurobehavioral assessment, Nrf2 nuclear expression, and the amount of inflammation factors were evaluated. Application of rTMS exhibited a significant antidepressant and anxiolytic-like effect, which was associated with the increased Nrf2 nuclear translocation and reduced level of TNF-α, iNOS, IL-1β, and IL-6 in the hippocampus. Following Nrf2 silencing, the antidepressant and anxiolytic-like effect produced by rTMS was abolished. Moreover, the elevated Nrf2 nuclear translocation, and the reduced production of TNF-α, iNOS, IL-1β, and IL-6 in hippocampus mediated by rTMS, were reversed by Nrf2 knockdown. Together, these results reveal that the Nrf2-induced anti-inflammation effect is crucial in regulating antidepressant-related behaviors produced by rTMS.

    更新日期:2020-01-07
  • C1q/TNF-related protein 4 induces signal transducer and activator of transcription 3 pathway and modulates food intake
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Yuejie Li; Liu Ye; Gongwei Jia; Hong Chen; Lehua Yu; Dandong Wu

    C1q/TNF-related Protein 4 (CTRP4) has been reported to decrease food intake and regulate energy homeostasis. However, its underlying mechanism and signaling pathway remain unknown. Using an adenovirus-mediated hypothalamic CTRP4 overexpression model, we investigated the impact of CTRP4 on food intake and signal transducer and activator of transcription 3 (STAT3) signaling pathway in normal chow-fed mice. Expressions of neuropeptides including proopiomelanocortin (POMC) and neuropeptide Y (NPY) were studied in hypothalamus by western blot and immunochemistry. STAT3 and suppressor of cytokine signaling 3 (SOCS3) were determined by western blot. STAT3 signaling pathway was also investigated in Neuro 2A (N2a) cells after CTRP4 overexpression intervention. We found that food intake decreased significantly in mice under normal chow condition after CTRP4 overexpression. Both immunohistochemistry and western blot demonstrated that POMC expression was significantly increased while NPY expression was significantly decreased. The changes of neuropeptides were accompanied by significant increased STAT3 phosphorylation and decreased SOCS3 levels. The same changes of neuropeptides and STAT3 signaling were also found in N2a cells after CTRP4 overexpression intervention. Collectively, our data reveals that CTRP4 induces the activation of STAT3 signaling and decreases food intake.

    更新日期:2020-01-07
  • Neural response selectivity to natural sounds in the bat midbrain
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Angeles Salles; Sangwook Park; Harshavardhan Sundar; Silvio Macías; Mounya Elhilali; Cynthia F. Moss

    Little is known about the neural mechanisms that mediate differential action-selection responses to communication and echolocation calls in bats. For example, in the big brown bat, FM food-claiming communication calls closely resemble FM echolocation calls, which guide social and orienting behaviors, respectively. Using advanced signal processing methods, we identified fine differences in temporal structure of these natural sounds that appear key to auditory discrimination and behavioral decisions. We recorded extracellular potentials from single neurons in the midbrain inferior colliculus of passively listening animals, and compared responses to playbacks of acoustic signals used by bats for social communication and echolocation. We combined information obtained from spike number and spike triggered averages to reveal a robust classification of neuron selectivity for communication or echolocation calls. These data highlight the importance of temporal acoustic structure for differentiating echolocation and food-claiming social calls and point to general mechanisms of natural sound processing across species.

    更新日期:2020-01-07
  • Priming of GABAergic long-term potentiation by muscarinic receptors
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Koyam Morales-Weil; Macarena Moreno; Juan Ahumada; Jorge Arriagada; Pablo Fuentealba; Christian Bonansco; Marco Fuenzalida
    更新日期:2020-01-07
  • Lysosomal dysregulation in the murine AppNL-G-F/NL-G-F model of Alzheimer’s disease
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Lauren S. Whyte; Sofia Hassiotis; Kathryn J. Hattersley; Kim M. Hemsley; John J. Hopwood; Adeline A. Lau; Timothy J. Sargeant

    Lysosomal network dysfunction is a prominent feature of Alzheimer’s disease. Although transgenic mouse models of Alzheimer’s disease are known to model some aspects of lysosomal network dysfunction, the lysosomal network has not yet been examined in the knock-in AppNL-G-F/NL-G-F mouse. We aimed to determine whether AppNL-G-F/NL-G-F mice exhibit disruptions to the lysosomal network in the brain. Lysosome-associated membrane protein 1 and cathepsins B, L and D accumulated at amyloid beta plaques in the AppNL-G-F/NL-G-F mice, as occurs in human Alzheimer’s patients. The accumulation of these lysosomal proteins occurred early in the development of neuropathology, presenting at the earliest and smallest amyloid beta plaques observed. AppNL-G-F/NL-G-F mice also exhibited elevated activity of β-hexosaminidase and cathepsins D/E and elevated levels of selected lysosomal network proteins, namely cathepsin D and LC3-II in the cerebral cortex, as determined by western blot. Elevation of cathepsin D did not change the extent of co-localisation between cathepsin D and lysosome-associated membrane protein 1 in the AppNL-G-F/NL-G-F mice. These findings demonstrate that perturbations of the lysosomal network occur in the AppNL-G-F/NL-G-F mouse model, further validating its use an animal model of pre-symptomatic Alzheimer’s disease.

    更新日期:2020-01-07
  • The Role of Circular RNAs in Brain Injury
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Huaxin Zhu; Zelong Xing; Yueyu Zhao; Zheng Hao; MeiHua Li

    Circular RNAs are an increasingly important topic in non-coding RNA biology, drawing considerable attention in recent years. Accumulating evidence suggests a critical role for circular RNAs in both early and latent stages of disease pathogenesis. Circular RNAs are abundantly expressed in brain tissue, with significant implications for neural development and disease progression. Disruption of these processes, including those seen in response to brain injury, can have serious consequences such as hemiplegia, aphasia, coma, and death. In this review, we describe the role of circular RNAs in the context of brain injury and explore the potential connection between circular RNAs, brain hypoxic ischemic injury, ischemia-reperfusion injury, and traumatic injury.

    更新日期:2020-01-07
  • Optical dissection of synaptic plasticity for early adaptation in Caenorhabditis elegans
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Keita Ashida; Hisashi Shidara; Kohji Hotta; Kotaro Oka

    To understand neuronal information processing, it is essential to investigate the input–output relationship and its modulation via detailed dissections of synaptic transmission between pre- and postsynaptic neurons. In Caenorhabditis elegans, pre-exposure to an odorant for five minutes reduces chemotaxis (early adaptation). AWC sensory neurons and AIY interneurons are crucial for this adaptation; AWC neurons sense volatile odors, and AIY interneurons receive glutamatergic inputs from AWC neurons. However, modulations via early adaptation of the input–output relationship between AWC and AIY are not well characterized. Here we use a variety of fluorescent imaging techniques to show that reduced synaptic-vesicle release without Ca2+ modulation in AWC neurons suppresses the Ca2+ response in AIY neurons via early adaptation. First, early adaptation modulates the Ca2+ response in AIY but not AWC neurons. Adaptation in the Ca2+ signal measured in AIY neurons is caused by adaptation in glutamate release from AWC neurons. Further, we found that a G protein γ-subunit, GPC-1, is related to modulation of glutamate input to AIY. Our results dissect the modulation of the pre- and postsynaptic relationship in vivo based on optical methods, and demonstrate the importance of neurotransmitter-release modulation in presynaptic neurons without Ca2+ modulation.

    更新日期:2020-01-07
  • Testing the limits of sex differences using variable stress
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Alyssa Johnson; Jennifer R. Rainville; G. Nicole Rivero-Ballon; Katerina Dhimitri; Georgia E. Hodes

    Depression is a chronic disease that affects nearly twice as many women as men, and symptoms can differ by sex. Preclinical models disproportionately use male subjects and test a single behavioral endpoint immediately at the cessation of stress. We conducted variable stress in male and female mice for 6, 28, and 56 days, and measured behavior with a battery chosen to match research domain criteria. To examine individual differences, we generated a composite z score to measure stress susceptibility across behavioral tests. We also tested behavior following a 30-day recovery period to evaluate the duration of the stress effects. Females, but not males, were susceptible to 6 days of variable stress when behavioral testing started 24 hours later. If behavioral testing was conducted 30 days later both males and females expressed stress related behaviors. Males and females were stress susceptible to 28 days of variable stress and effects were long lasting. Both sexes habituated to 56 days of variable stress, but anxiety associated measures still showed persistence. Performance on specific behavioral tests was often different between individuals and between sexes, and not all stressed animals were susceptible to all tested behaviors. These studies confirm that behavioral sex differences are detected in response to variable stress, and reveal information about individual differences. Use of a test battery that measures varying endophenotypes can be combined into a single stress susceptibility score as a tool similar to the scales/inventories used for the study of depression in humans. We present these data with the goal of furthering the field’s understanding sex differences and how they shape the biology of mood disorders.

    更新日期:2020-01-07
  • Mechanisms of impulsive responding to temporally predictable events as revealed by EMG
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Inga Korolczuk; Boris Burle; Jennifer T Coull; Kamila Smigasiewicz

    Temporal predictability optimises behaviour when a simple response is required, as demonstrated by faster reaction times and higher accuracy. However, its beneficial effects come at a cost under situations of response conflict. Here, we investigated the motor underpinnings of behaviour to temporally predictable events in the Simon conflict task. We compared motor responses to lateralised targets whose position conflicted (incompatible condition) or not (compatible condition) with the hand of response. Importantly, electromyographic (EMG) recordings allowed us to study “partial errors”, defined as subthreshold muscle activity in the incorrect response agonist preceding a correct response. Advanced distributional analyses coupled with EMG data revealed that temporal predictability induced impulsive premature responding, as indexed by increased likelihood of fast incorrect EMG activations (both partial errors and errors) to incompatible targets. In parallel, responding to temporally predictable targets speeded the latency of partial errors, further indicating that temporal predictability increased the tendency to act prematurely. There was, however, no effect of temporal predictability on subsequent suppression of partial errors. Our results provide direct evidence that temporal predictability acts by increasing the urge to initiate a fast, yet potentially erroneous, response. This mechanism parsimoniously explains both beneficial effects of temporal predictability when no conflict in the environment is present, as well as its costs when more complex motor behaviour is required.

    更新日期:2020-01-07
  • Low-intensity, Kilohertz Frequency Spinal Cord Stimulation Differently Affects Excitatory and Inhibitory Neurons in the Rodent Superficial Dorsal Horn
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Kwan Yeop Lee; Chilman Bae; Dongchul Lee; Zachary Kagan; Kerry Bradley; Jin Mo Chung; Jun-Ho La

    Since 1967, spinal cord stimulation (SCS) has been used to manage chronic intractable pain of the trunk and limbs. Compared to traditional high-intensity, low-frequency (<100 Hz) SCS that is thought to produce paresthesia and pain relief by stimulating large myelinated fibers in the dorsal column (DC), low-intensity, high-frequency (10 kHz) SCS has demonstrated long-term pain relief without generation of paresthesia. To understand this paresthesia-free analgesic mechanism of 10 kHz SCS, we examined whether 10 kHz SCS at intensities below sensory thresholds would modulate spinal dorsal horn (DH) neuronal function in a neuron type-dependent manner. By using in vivo and ex vivo electrophysiological approaches, we found that low-intensity (sub-sensory threshold) 10 kHz SCS, but not 1 kHz or 5 kHz SCS, selectively activates inhibitory interneurons in the spinal DH. This study suggests that low-intensity 10 kHz SCS may inhibit pain sensory processing in the spinal DH by activating inhibitory interneurons without activating DC fibers, resulting in paresthesia-free pain relief.

    更新日期:2020-01-07
  • Sleep loss immediately after fear memory reactivation attenuates fear memory reconsolidation
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Rishi Sharma; Pradeep Sahota; Mahesh M. Thakkar

    Permanently stored memories become labile through a process called reactivation. Once reactivated, these memories need reconsolidation to become permanent. Sleep is critical for memory consolidation. Is sleep necessary for memory reconsolidation? We hypothesized that sleep loss immediately after fear reactivation (FR) will prevent memory reconsolidation. To test our hypothesis, two experiments were performed in adult male C57BL/6J mice exposed to contextual fear conditioning paradigm with inescapable foot shock as unconditional stimulus (US) and contextual cage as conditional stimulus (CS). Sleep loss was achieved either by 5 hours of sleep deprivation (SD; Experiment 1) or by systemic infusion of modafinil (200 mg/Kg, ip), an FDA approved wake-promoting agent (Experiment 2). One hour after light-onset, fear memory acquisition (FMA) was performed on Day 1. Mice were allowed to explore CS for 5 min followed by presentation of US (7 foot-shocks; 0.5 mA, 2.0 s duration) at pseudorandom intervals. Controls were exposed to similar CS but no shocks were delivered. On Day 2, mice were exposed to CS for 2 min (without US; for FR) followed by either sleep loss or no sleep loss. On Day 3, Fear memory recall (FMR) was performed by exposing mice to CS (without US) for 12 min. Percent time spent in freezing was monitored during FC, FR and FMR. Our results suggested that as compared to sleeping controls, mice with sleep loss immediately after FR displayed a significant reduction in percent time freezing during FMR. These results suggest that sleep loss may prevent memory reconsolidation.

    更新日期:2020-01-07
  • Acute and repeated intranasal oxytocin differentially modulate brain-wide functional connectivity
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Marco Pagani; Alessia De Felice; Caterina Montani; Alberto Galbusera; Francesco Papaleo; Alessandro Gozzi

    Central release of the neuropeptide oxytocin (OXT) modulates neural substrates involved in socio-affective behavior. This property has prompted research into the use of intranasal OXT administration as an adjunctive therapy for brain conditions characterized by social impairment, such as autism spectrum disorders (ASD). However, the neural circuitry and brain-wide functional networks recruited by intranasal OXT administration remain elusive. Moreover, little is known of the neuroadaptive cascade triggered by long-term administration of this peptide at the network level. To address these questions, we applied fMRI-based circuit mapping in adult mice upon acute and repeated (seven-day) intranasal dosing of OXT. We report that acute and chronic OXT administration elicit comparable fMRI activity as assessed with cerebral blood volume mapping, but entail largely different patterns of brain-wide functional connectivity. Specifically, acute OXT administration focally boosted connectivity within key limbic components of the rodent social brain, whereas repeated dosing led to a prominent and widespread increase in functional connectivity, involving a strong coupling between the amygdala and extended cortical territories. Importantly, this connectional reconfiguration was accompanied by a paradoxical reduction in social interaction and communication in wild-type mice. Our results identify the network substrates engaged by exogenous OXT administration, and show that repeated OXT dosing leads to a substantial reconfiguration of brain-wide connectivity, entailing an aberrant functional coupling between cortico-limbic structures involved in socio-communicative and affective functions. Such divergent patterns of network connectivity might contribute to discrepant clinical findings involving acute or long-term OXT dosing in clinical populations.

    更新日期:2020-01-07
  • Maternal deprivation and sexalter central levels of neurotrophins and inflammatory cytokines in rats exposed to palatable food in adolescence
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Roberta Ströher; Carla de Oliveira; Dirson João Stein; Isabel Cristina de Macedo; Jéferson Ferraz Goularte; Lisiane Santos da Silva; Gabriela Gregory Regner; Helouise Richardt Medeiros; Wolnei Caumo; Iraci L.S. Torres

    Maternal deprivation(MD) in rodents is used to simulate human-infant early life stress, which leads to neural, hormonal, and behavioral alterations. Palatable food(PF) can reduce the stress response, and individuals use it as a self-applied stress relief method. Thus, the present study aimed to evaluatethe effect of the association between MD in the early life (P1–P10) and PF consumption (condensed milk, P21–P44) in the central neuroplasticity (BDNF/NGF levels) and central neuroinflammatory parameters (TNF-α, IL-6, and IL-10 levels) in male and female Wistar rats in the adolescence. In addition, weight-related parameters(weight gain, Lee Index, and relative adipose tissue weight) were evaluated. PF exposure increased relative adipose tissue weight; however,it did not lead to a change in animals’ body weight. MD reduced hypothalamic BDNF and NGF levels, and hippocampalTNF-α levels in male and female rats. Animals of both sexes that received PF, exhibited reduced hypothalamic NGF levels. Neuroinflammatory marker evaluations showed that male rats were more susceptible to the interventions than female rats, since MD reduced their cortical IL-10 levels and PF increased their IL-6 levels. Differences in the Lee index, central BDNF, TNF-α, and IL-6levels were observed between sexes. Male animals per se presented greater Lee index. Female rats had higher BDNF and IL-6 levels in the hippocampus and hypothalamus and higher hypothalamic TNF-α levels than those observed in males. In conclusion, there were more noticeable effects of MD than PF on the variables measured in this study.Sex effect was identified as an important factor and influenced most of the neurochemical measures in this study. In this way, we suggest including both female and male animals in researches to improve the quality of translational studies.

    更新日期:2020-01-07
  • Coupled Temporal Fluctuation and Global Signal Synchronization of Spontaneous Brain Activity in Hypnosis for Respiration Control: An fMRI Study
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Yanjun Liu; Yini He; Rongmao Li; Shaode Yu; Jianyang Xu; Yaoqin Xie
    更新日期:2020-01-07
  • Metabotropic Glutamate Receptors at the Aged Mossy Fiber – CA3 synapse of the hippocampus
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Ernesto Griego; Emilio J. Galván

    Metabotropic glutamate receptors (mGluRs) are a group of G-protein-coupled receptors that exert a broad array of modulatory actions at excitatory synapses of the central nervous system. In the hippocampus, the selective activation of the different mGluRs modulates the intrinsic excitability, the strength of synaptic transmission, and induces multiple forms of long-term plasticity. Despite the relevance of mGluRs in the normal function of the hippocampus, we know very little about the changes that mGluRs functionality undergoes during the non-pathological aging. Here, we review data concerning the physiological actions of mGluRs, with particular emphasis on hippocampal area CA3. Later, we examine changes in the expression and functionality of mGluRs during the aging process. We complement this review with original data showing an array of electrophysiological modifications observed in the synaptic transmission and intrinsic excitability of aged CA3 pyramidal cells in response to the pharmacological stimulation of the different mGluRs.

    更新日期:2020-01-07
  • EphrinB/EphB signaling contributes to the synaptic plasticity of chronic migraine through NR2B phosphorylation
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Jiang Wang; Zhaoyang Fei; Jie Liang; Xue Zhou; Guangcheng Qin; Dunke Zhang; Jiying Zhou; Lixue Chen

    The specific mechanism of migraine chronification remains unclear. We previously demonstrated that synaptic plasticity was associated with migraine chronification. EphB receptors and their ligands, ephrinBs, are considered to be key molecules regulating the synaptic plasticity of the central nervous system. However, whether they can promote the chronification of migraine by regulating synaptic plasticity is unknown. Therefore, we investigated the role of ephrinB/EphB signaling in chronic migraine (CM). Male Sprague-Dawley rats were used to construct a chronic migraine model by dural infusion of an inflammatory soup for 7 days. We used qPCR, western blot, and immunofluorescence to detect the mRNA and protein levels of EphB2 and ephrinB2. The paw withdrawal latency and paw withdrawal threshold were measured after lateral ventricle treatment with EphB1-Fc (an inhibitor of EphB receptor). Changes in synaptic plasticity were explored by examining synaptic-associated proteins by western blot, dendritic spines of neurons by Golgi-Cox staining, and synaptic ultrastructure by transmission electron microscopy. We found that the expression of EphB2 and ephrinB2 was increased in CM. The administration of EphB1-Fc relieved hyperalgesia and changes in synaptic plasticity induced by CM. In addition, EphB1-Fc inhibited the upregulation of NR2B phosphorylation. These results indicate that ephrinB/EphB signaling may regulate synaptic plasticity in CM via NR2B phosphorylation, which suggests the novel idea that ephrinB/EphB signaling may be a target for the treatment of migraine chronification.

    更新日期:2020-01-07
  • Effects of small temperature differences detected in callosal circuits of the anterior cingulate cortex
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    R. Cotter; S. Winnik; A. Singer; G. Aaron

    We measured the sensitivity of cortical circuit activity to small differences in local cortical environments by studying how temperature affects the trajectory of epileptiform events (EEs). EEs evoked via blockade of GABA-A receptors were recorded extracellularly from mouse coronal brain slices containing both hemispheres of anterior cingulate cortex synaptically connected by corpus callosum axons. Preferentially illuminating one hemisphere with the microscope condenser produced temperature differences of 0.1°C between the hemispheres. The relatively warmer hemisphere typically initiated the EEs that then propagated to the contralateral side, demonstrating temperature directed propagation. Severing the callosum following one hour of EEs showed that the warmer hemisphere possessed a higher rate of EE generation. Further experiments implied that intact callosal circuits were required for the increased EE generation in the warmer hemisphere. We propose a hypothesis whereby callosal circuits can amplify differences in respective hemispheric activity, promoting this directionality in seizure propagation.

    更新日期:2020-01-07
  • Enduring and sex-specific changes in hippocampal gene expression after a subchronic immune challenge
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Daria Tchessalova; Natalie C. Tronson

    Major illnesses, including heart attack and sepsis, can cause cognitive impairments, depression, and progressive memory decline that persist long after recovery from the original illness. In rodent models of sepsis or subchronic immune challenge, memory deficits also persist for weeks or months, even in the absence of ongoing neuroimmune activation. This raises the question of what mechanisms in the brain mediate such persistent changes in neural function. Here, we used RNA-sequencing as a large-scale, unbiased approach to identify changes in hippocampal gene expression long after a subchronic immune challenge previously established to cause persistent memory impairments in both males and females. We observed enduring dysregulation of gene expression three months after the end of a subchronic immune challenge. Surprisingly, there were striking sex differences in both the magnitude of changes and the specific genes and pathways altered, where males showed persistent changes in both immune- and plasticity-related genes three months after immune challenge, whereas females showed few such changes. In contrast, females showed striking differential gene expression in response to a subsequent immune challenge. Thus, immune activation has enduring and sex-specific consequences for hippocampal gene expression and the transcriptional response to subsequent stimuli. Together with findings of long-lasting memory impairments after immune challenge, these data suggest that illnesses can cause enduring vulnerability to, cognitive decline, affective disorders, and memory impairments via dysregulation of transcriptional processes in the brain.

    更新日期:2020-01-07
  • Time Course of Inflammation in Dorsal Root Ganglia Correlates with Differential Reversibility of Mechanical Allodynia
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Myung-chul Noh; Benjamin Mikler; Twinkle Joy; Peter A. Smith
    更新日期:2020-01-07
  • Enkephalinergic Circuit Involved in Nociceptive Modulation in the Spinal Dorsal Horn
    Neuroscience (IF 3.244) Pub Date : 2020-01-07
    Yang Bai; Meng-Ying Li; Jiang-Bo Ma; Jia-Ni Li; Xiao-Yu Teng; Ying-Biao Chen; Jun-Bin Yin; Jing Huang; Jing Chen; Ting Zhang; Xin-Tong Qiu; Tao Chen; Hui Li; Sheng-Xi Wu; Ya-Nan Peng; Xiang Li; Zhen-Zhen Kou; Yun-Qing Li
    更新日期:2020-01-07
  • Neuropeptide Y signaling in the lateral hypothalamus modulates diet component selection and is dysregulated in a model of diet-induced obesity
    Neuroscience (IF 3.244) Pub Date : 2019-12-27
    M.C.R. Gumbs; L. Eggels; T. Kool; U.A. Unmehopa; J.K. van den Heuvel; K. Lamuadni; J.D. Mul; S.E. la Fleur
    更新日期:2019-12-27
  • Swimming physical training prevented the onset of acute muscle pain by a mechanism dependent of PPARγ receptors and CINC-1
    Neuroscience (IF 3.244) Pub Date : 2019-12-27
    Graciana de Azambuja; Beatriz Botasso Gomes; Leonardo Henrique Dalcheco Messias; Bruna de Melo Aquino; Carolina Ocanha Jorge; Fúlvia de Barros Manchado Gobatto; Maria Cláudia Gonçalves de Oliveira Fusaro

    Regular physical exercise has been described as a good strategy for prevention or reduction of musculoskeletal pain. The Peroxisome Proliferator-Activated Receptor Gamma (PPARγ) has been investigated as a promising target for the control of inflammatory pain. Therefore, the aim of this study was to evaluate whether activation of PPARγ receptors is involved in the reduction of acute muscle pain by chronic exercise and, in this case, whether this process is modulated by inflammatory cytokines. To this end, Wistar rats were submitted to swimming physical training for a period of 10 weeks, 5 days per week, 40 minutes/day, in an intensity of 4% of the body mass. Muscle hyperalgesia was measured by Randall Selitto test and pro-inflammatory cytokines were quantified by ELISA. The results showed that swimming physical training prevented the onset of acute mechanical muscle hyperalgesia and the increase in muscle levels of Cytokine-induced neutrophil chemoattractant 1 (CINC-1) induced by carrageenan into gastrocnemius muscle. In addition, local pre-treatment with the selective PPARγ receptors antagonist GW9662 reversed the mechanical muscle hypoalgesia and the modulation of CINC-1 levels induced by swimming physical training. These data suggest that swimming physical training prevented the onset of acute mechanical muscle hyperalgesia by a mechanism dependent of PPARγ receptors, which seems to contribute to this process by modulation of the pro-inflammatory cytokine CINC-1, and highlight the potential of PPARγ receptors as a target to control musculoskeletal pain and to potentiate the reduction of musculoskeletal pain induced by exercise.

    更新日期:2019-12-27
  • Profiling the expression of endoplasmic reticulum stress associated heat shock proteins in animal epilepsy models
    Neuroscience (IF 3.244) Pub Date : 2019-12-27
    Marta Nowakowska; Fabio Gualtieri; Eva-Lotta von Rüden; Florian Hansmann; Wolfgang Baumgärtner; Andrea Tipold; Heidrun Potschka

    Unfolded protein response is a signaling cascade triggered by misfolded proteins in the endoplasmic reticulum. Heat shock protein H4 (HSPH4) and A5 (HSPA5) are two chaperoning proteins present within the organelle, which target misfolded peptides during prolonged stress conditions. Epileptogenic insults and epileptic seizures are a notable source of stress on cells. To investigate whether they influence expression of these chaperones, we performed immunohistochemical stainings in brains from rats that experienced a status epilepticus (SE) as a trigger of epileptogenesis and from canine epilepsy patients. Quantification of HSPA5 and HSPH4 revealed alterations in hippocampus and parahippocampal cortex. In rats, SE induced up-regulation of HSPA5 in the piriform cortex and down-regulation of HSPA5 and HSPH4 in the hippocampus. Regionally restricted increases in expression of the two proteins has been observed in the chronic phase with spontaneous recurrent seizures. Confocal microscopy revealed a predominant expression of both proteins in neurons, no expression in microglia and circumscribed expression in astroglia. In canine patients, only up-regulation of HSPH4 expression was observed in Cornu Ammonis 1 region in animals diagnosed with structural epilepsy. This characterization of HSPA5 and HSPH4 expression provided extensive information regarding spatial and temporal alterations of the two proteins during SE-induced epileptogenesis and following epilepsy manifestations. Up-regulation of both proteins implies stress exerted on ER during these disease phases. Taken together suggest a differential impact of epileptogenesis on HSPA5 and HSPH4 expression and indicate them as a possible target for pharmacological modulation of unfolded protein response.

    更新日期:2019-12-27
  • Region-specific effects of maternal separation on perineuronal net and parvalbumin-expressing interneuron formation in male and female rats
    Neuroscience (IF 3.244) Pub Date : 2019-12-27
    Kelsea R. Gildawie; Jennifer A. Honeycutt; Heather C. Brenhouse

    Early life experiences play a vital role in contributing to healthy brain development. Adverse experiences have a lasting impact on the prefrontal cortex (PFC) and basolateral amygdala (BLA), brain regions associated with emotion regulation. Early life adversity via maternal separation (MS) has sex-specific effects on expression of parvalbumin (PV), which is expressed in fast-spiking GABAergic interneurons that are preferentially enwrapped by perineuronal nets (PNNs). Importantly, PNN formation coincides with the closure of developmental critical periods and regulates PV-expressing interneuron activity. Since aberrant PNN organization has been reported following adverse experiences in adolescent and adult rats, we investigated the impact of adversity early in life in the form of MS on the developing brain. Rat pups were separated from their dams for 4 hours per day from postnatal day (P) 2-20. Tissue sections from juvenile (P20), adolescent (P40), and early adult (P70) animals containing the PFC and BLA were fluorescently stained to visualize Wisteria floribunda agglutinin+ PNNs and PV-expressing interneurons, and density and intensity was quantified. Our results confirm past reports that PFC PNNs form gradually throughout development; however, PNN density plateaus in adolescence, while intensity continues to increase into adulthood. Importantly, MS delays PNN formation in the prelimbic PFC and results in sex-specific aberrations in PNN structural integrity that do not appear until adulthood. The present findings reveal sex-, age-, and region-specific effects of early life adversity on PNN and PV maturation, implicating neuroplastic alterations following early life adversity that may be associated with sex differences in psychopathology and resilience.

    更新日期:2019-12-27
  • Noise-Induced Cochlear Synaptopathy With and Without Sensory Cell Loss
    Neuroscience (IF 3.244) Pub Date : 2019-12-27
    Katharine A. Fernandez; Dan Guo; Steven Micucci; Victor De Gruttola; M. Charles Liberman; Sharon G. Kujawa

    Prior work has provided extensive documentation of threshold sensitivity and sensory hair cell losses after noise exposure. It is now clear, however, that cochlear synaptic loss precedes such losses, at least at low-moderate noise doses, silencing affected neurons. To address questions of whether, and how, cochlear synaptopathy and underlying mechanisms change as noise dose is varied, we assessed cochlear physiologic and histologic consequences of a range of exposures varied in duration from 15 minutes to 8 hours and in level from 85 to 112 dB SPL. Exposures delivered to adult CBA/CaJ mice produced acute elevations in hair cell- and neural- based response thresholds ranging from trivial (∼5 dB) to large (∼50 dB), followed by varying degrees of recovery. Males appeared more noise vulnerable for some conditions of exposure. There was little to no inner hair cell (IHC) loss, but outer hair cell (OHC) loss could be substantial at highest frequencies for highest noise doses. Synapse loss was an early manifestation of noise injury and did not scale directly with either temporary or permanent threshold shift. With increasing noise dose, synapse loss grew to ∼50%, then declined for exposures yielding permanent hair cell injury/loss. All synaptopathic, but no non-synaptopathic exposures produced persistent neural response amplitude declines; those additionally yielding permanent OHC injury/loss also produced persistent reductions in OHC-based responses and exaggerated neural amplitude declines. Findings show that widespread cochlear synaptopathy can be present with and without noise-induced sensory cell loss and that differing patterns of cellular injury influence synaptopathic outcomes.

    更新日期:2019-12-27
  • Decreased glutamatergic synaptic strength in the periaqueductal gray contributes to maintenance of visceral pain in male rats with experimental pancreatitis
    Neuroscience (IF 3.244) Pub Date : 2019-12-27
    Qiaoling Liu; Chih-Yuan Ko; Chen Zheng; Lichao Ye; Bo Liu; Hongzhi Gao; Donghong Huang; Dylan Chou

    Visceral pain originating from chronic inflammation of the pancreas is often intractable and difficult to manage clinically. However, the pathogenesis of the central nervous system underlying visceral pain is still poorly understood. The aim of the present study was to investigate the role of the midbrain ventrolateral periaqueductal gray (vlPAG) in a rat model of chronic visceral pain induced by pancreatitis. In the present study, we used a well-established rat model of chronic pancreatitis induced by tail vein injection of dibutyltin dichloride (DBTC). To assess the DBTC-induced visceral pain, we examined the abdominal withdrawal by von Frey filament test. We further studied the synaptic transmission in the vlPAG by whole-cell patch-clamp electrophysiological recordings. Rats receiving DBTC injection exhibited a significantly increased withdrawal frequency to mechanical stimulation of the abdomen compared to rats injected with vehicle. Interestingly, compared to rats injected with vehicle, we found that neurons dissected from DBTC-treated rats exhibited a significantly decreased synaptic strength, which was revealed by a diminishedα-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid/ N-methyl-D-aspartic acid (AMPA/NMDA) ratio in the vlPAG. Moreover, our results further demonstrated that neurons obtained from DBTC-treated rats displayed a higher paired-pulse ratio, as well as less frequent and smaller amplitudes of miniature excitatory postsynaptic currents in the vlPAG compared to rats injected with vehicle. Furthermore, intra-vlPAG microinjection of AMPA alleviated DBTC-induced abdominal hypersensitivity. Taken together, our findings suggest that diminished glutamatergic synaptic strength via both presynaptic and postsynaptic mechanisms in the midbrain vlPAG is associated with DBTC-induced abdominal hypersensitivity. In addition, activation of AMPA receptors in the vlPAG alleviates DBTC-induced abdominal hypersensitivity.

    更新日期:2019-12-27
  • Neuroprotective action of teriflunomide in a mouse model of transient middle cerebral artery occlusion
    Neuroscience (IF 3.244) Pub Date : 2019-12-27
    Zhengfang Lu; Di Zhang; Kefei Cui; Xiaojie Fu; Jiang Man; Hong Lu; Lie Yu; Yufeng Gao; Xianliang Liu; Linghui Liao; Xiang Li; Chang Liu; Yongxin Zhang; Zhen Zhang; Jianping Wang

    Teriflunomide has been reported to inhibit microglial activation in experimental models of traumatic brain injury. However, its roles in ischemic stroke and underlying mechanisms of action are still undiscovered. In this study, we investigated the effects of teriflunomide on brain edema, neurologic deficits, infarct volume, neuroinflammation, blood-brain barrier (BBB) permeability, and neurogenesis in a mouse model of transient middle cerebral artery occlusion (tMCAO). tMCAO mice treated with teriflunomide showed lower brain water content on day 3, milder neurologic deficits and smaller infarct volume on day 7 than those treated with vehicle. Additionally, mice received teriflunomide had fewer activated Iba-1-positive microglia and lower protein levels of interleukin-1β (IL-1β), cyclooxygenase-2 (COX-2), and 3-Nitrotyrosine (3-NT) compared with those received vehicle on day 3. Further, teriflunomide alleviated Evans blue dye leakage, increased pericyte coverage and protein levels of platelet-derived growth factor B (PDGFB), platelet-derived growth factor receptor β (PDGFRβ) and Bcl2, and decreased the number of PDGFRβ/matrix metalloproteinase 9 (MMP9)-positive cells. Moreover, teriflunomide reduced the loss of zonula occludens-1 (ZO-1) and occludin. Finally, teriflunomide significantly upregulated the number of 5-bromo-20-deoxyuridine (BrdU)/ doublecortin(DCX)-positive cells and expression of mammalian achaete-scute homolog 1 (Mash1), DCX and Pbx1 in subventricular zone (SVZ) on day 7 after stroke. Our results indicate that teriflunomide exhibits protective roles in ischemic stroke by inhibiting neuroinflammation, alleviating BBB disruption and enhancing neurogenesis.

    更新日期:2019-12-27
  • Modified glutamatergic postsynapse in neurodegenerative disorders
    Neuroscience (IF 3.244) Pub Date : 2019-12-27
    Bruno José Moraes; Patrícia Coelho; Lígia Fão; Ildete Luísa Ferreira; A. Cristina Rego

    The postsynaptic density (PSD) is a complex subcellular domain important for postsynaptic signaling, function, and plasticity. The PSD is present at excitatory synapses and specialized to allow for precise neuron-to-neuron transmission of information. PSD is localized immediately underneath the postsynaptic membrane forming a major protein network that regulates postsynaptic signaling and synaptic plasticity. Glutamatergic synaptic dysfunction affecting PSD morphology and signaling events have been described in many neurodegenerative disorders, either sporadic or familial forms. Thus, in this review we describe the main protein players forming the PSD and their activity, as well as relevant modifications in key components of the postsynaptic architecture occurring in Huntington’s, Parkinson’s and Alzheimer’s diseases.

    更新日期:2019-12-27
  • 更新日期:2019-12-27
  • Abnormal Pain Sensation in Mice Lacking the Prokineticin Receptor PKR2: Interaction of PKR2 with Transient Receptor Potential TRPV1 and TRPA1
    Neuroscience (IF 3.244) Pub Date : 2019-12-26
    Daniela Maftei; Vittorio Vellani; Marco Artico; Chiara Giacomoni; Cinzia Severini; Roberta Lattanzi

    The amphibian Bv8 and the mammalian prokineticin 1 (PROK1) and 2 (PROK2) are new chemokine-like protein ligands acting on two G protein-coupled receptors, prokineticin receptor 1 (PKR1) and 2 (PKR2), participating to the mediation of diverse physiological and pathological processes. Prokineticins (PKs), specifically activating the prokineticin receptors (PKRs) located in several areas of the central and peripheral nervous system associated with pain, play a fundamental role in nociception. In this paper, to improve the understanding of the prokineticin system in the neurobiology of pain, we investigated the role of PKR2 in pain perception using pkr2 gene-deficient mice. We observed that, compared to wildtype, pkr2-null mice were more resistant to nociceptive sensitization to temperatures ranging from 46 to 48 °C, to capsaicin and to protons, highlighting a positive interaction between PKR2 and the non-selective cation channels TRPV1. Moreover, PKR2 knock-out mice showed reduced nociceptive response to cold temperature (4 °C) and to mustard oil-induced inflammatory hyperalgesia, suggesting a functional interaction between PKR2 and transient receptor potential ankyrin 1 ion (TRPA1) channels. This notion was supported by experiments in dorsal root ganglia (DRG) cultures from pkr1–pkr2-null mice, demonstrating that the percentage of Bv8-responsive DRG neurons which were also responsive to mustard oil was much higher in PKR1−/− than in PKR2−/− mice. Taken together, these findings suggest a functional interaction between PKR2 and TRP channels in the development of hyperalgesia. Drugs able to directly or indirectly block these targets and/or their interactions may represent potential analgesics.

    更新日期:2019-12-27
  • High fructose diet induces sex-specific modifications in synaptic respiration and affective-like behaviors in rats
    Neuroscience (IF 3.244) Pub Date : 2019-12-24
    Alix Kloster; Molly M. Hyer; Samya Dyer; Charlie Salome-Sanchez; Gretchen N. Neigh

    The consequences of excessive fructose intake extend beyond those of metabolic disorder to changes in emotional regulation and cognitive function. Long-term consumption of fructose, particularly common when begun in adolescence, is more likely to lead to deleterious consequences than acute consumption. These long-term consequences manifest differently in males and females, suggesting a sex-divergent mechanism by which fructose can impair physiology and neural function. The purpose of the current project was to investigate a possible sex-specific mechanism by which elevated fructose consumption drives behavioral deficits and accompanying metabolic symptoms – specifically, synaptic mitochondrial function. Male and female rats were fed a high fructose diet beginning at weaning and maintained into adulthood. Measures of physiological health across the diet consumption period indicated that females were more likely to gain weight than males while both displayed increased circulating blood glucose. As adults, females fed the high fructose diet displayed increased floating behavior in the forced swim task (FST) while males exhibited increased exploratory behavior in the open field. Synaptic respiration was altered by diet in both females and males but the effect was sex-divergent – fructose-fed females had increased synaptic respiration while males showed a decrease. When exposed to an acute energetic challenge, the pattern was reversed. Taken together, these data indicate that diet-induced alterations to neural function and physiology are sex-specific and highlight the need to consider sex as a biological variable when treating metabolic disease. Furthermore, these data suggest that synaptic mitochondrial function may contribute directly to the behavioral consequences of elevated fructose consumption.

    更新日期:2019-12-25
  • RAMP1 and RAMP3 differentially control amylin’s effects on food intake, glucose and energy balance in male and female mice
    Neuroscience (IF 3.244) Pub Date : 2019-12-24
    Bernd Coester; Sydney W. Pence; Soraya Arrigoni; Christina N. Boyle; Christelle Le Foll; Thomas A. Lutz
    更新日期:2019-12-25
  • Early postnatal ethanol exposure in mice induces sex-dependent memory impairment and reduction of hippocampal NMDA-R2B expression in adulthood
    Neuroscience (IF 3.244) Pub Date : 2019-12-23
    Alessandro Ieraci; Daniel G. Herrera

    Drinking alcohol during pregnancy is particularly detrimental for the developing brain and may cause a broad spectrum of cognitive and behavioral impairments, collectively known as fetal alcohol spectrum disorders (FASD). While behavioral abnormalities and brain damage have been widely investigated in animal models of FASD, the sex differences in the vulnerability to perinatal ethanol exposure have received less consideration. Here we investigated the long-term behavioral and molecular effects of acute ethanol-binge like exposure during the early postnatal period (equivalent to the third trimester of human pregnancy) in adult male and female mice. CD1 mice received a single ethanol exposure on P7 and were analyzed starting from P60. We found that ethanol-exposed mice showed increased activity in the open field test and in the plus-maze test, regardless of the sex. Interestingly, only ethanol-exposed adult male mice exhibited memory impairment in the water maze and fear-conditioning tests. Remarkably, hippocampal levels of NMDA-R2B were reduced only in ethanol-exposed male, while total BDNF levels were increased in both male and female ethanol-exposed mice. Our data suggest a different susceptibility of early postnatal ethanol exposure in male and female CD1 mice.

    更新日期:2019-12-23
  • Individual differences in amphetamine locomotor sensitization are accompanied with changes in dopamine release and firing pattern in the dorsolateral striatum of rats
    Neuroscience (IF 3.244) Pub Date : 2019-12-23
    Gatica RI; Aguilar-Rivera MI; Azocar VH; Fuentealba JA

    Not all the people that consume drugs of abuse develop addiction. In this sense, just a percentage of rats express locomotor sensitization after repeated psychostimulant exposure. Neurochemical evidence has shown that locomotor sensitization is associated with changes in dorsolateral striatum (DLS) activity. However, it is unknown if individual differences observed in locomotor sensitization are related to differential neuro-adaptations in DLS activity. In this study, we measured basal dopamine (DA) levels and single unit activity in the DLS of anesthetized rats, after repeated amphetamine (AMPH) administration. Rats were treated with AMPH 1.0 mg/kg ip or saline ip for 5 days. Following 5 days of withdrawal, a challenge dose of AMPH 1.0 mg/kg ip was injected. In-vivo microdialysis experiments and single unit recording were carried out twenty-four hours after the last AMPH injection. Sensitized rats showed increased basal DA levels and baseline firing rate of medium spiny neurons (MSNs) compared to non-sensitized rats. The local variation index (Lv) was used to measure the firing pattern of MSNs. In saline rats, a bursty firing pattern was observed in MSNs. A decrease in MSNs baseline Lv accompanies the expression of AMPH locomotor sensitization. Moreover, a decrease in Lv after an acute AMPH 1.0 mg/kg injection was only observed in saline and sensitized rats. Our results show individual differences in DLS basal DA levels and firing pattern after repeated AMPH administration, suggesting that an hyperfunction of nigrostriatal pathway, accompanied by a decrease in DLS MSNs firing irregularity underlies the expression of AMPH locomotor sensitization.

    更新日期:2019-12-23
  • Characterizing the mechanical properties of ectopic axonal receptive fields in inflamed nerves and following axonal transport disruption
    Neuroscience (IF 3.244) Pub Date : 2019-12-23
    George Goodwin; Geoffrey M Bove; Bryony Dayment; Andrew Dilley

    Radiating pain is a significant feature of chronic musculoskeletal pain conditions such as radiculopathies, repetitive motion disorders and whiplash associated disorders. It is reported to be caused by the development of mechanically-sensitive ectopic receptive fields along intact nociceptor axons at sites of peripheral neuroinflammation (neuritis). Since inflammation disrupts axonal transport, we have hypothesised that anterogradely-transported mechanically sensitive ion channels accumulate at the site of disruption, which leads to axonal mechanical sensitivity (AMS). In this study, we have characterised the mechanical properties of the ectopic axonal receptive fields and have examined the contribution of mechanically sensitive ion channels to the development of AMS following neuritis and vinblastine-induced axonal transport disruption. In both models, there was a positive force-discharge relationship and mechanical thresholds were low (∼9 mN/mm2). All responses were attenuated by ruthenium red and FM1-43, which block mechanically sensitive ion channels. In both models, the transport of TRPV1 and TRPA1 was disrupted, and intraneural injection of agonists of these channels caused responses in neurons with AMS following neuritis but not vinblastine treatment. In summary, these data support a role for mechanically sensitive ion channels in the development of AMS.

    更新日期:2019-12-23
  • Industriousness moderates the link between default mode network subsystem and creativity
    Neuroscience (IF 3.244) Pub Date : 2019-12-23
    Tengbin Huo; Yiman Li; Kaixiang Zhuang; Li Song; Xiao Wang; Zhiting Ren; Qiang Liu; Wenjing Yang; Jiang Qiu

    Creativity has been consistently linked to the default mode network (DMN) and conscientiousness. However, the specific core regions that are involved in the relationship between the DMN and creativity and the manner in which conscientiousness influences the neural mechanism that underlies creativity remain unexplored. Therefore, in the present study, we used a combination of graph theory techniques and affinity propagation clustering (APC) to identify the core subnetworks of the DMN that are related to creativity and examine predictive relationships between creativity and resting-state functional connectivity (RSFC). Additionally, the moderating role that two lower-order facets of conscientiousness, namely, industriousness and orderliness, play in this relationship was explored. The results showed that creativity was positively associated with the within-module degree (WMD) of one subnetwork of DMN (i.e., DMN2) and that industriousness was the only facet of conscientiousness that moderated this relationship. Specifically, creativity could be successfully predicted from the RSFC between DMN2 regions and all DMN regions in the high-industriousness group but not the low-industriousness group. Taken together, these results suggest that a core DMN subnetwork is crucial for creativity and that industriousness moderates the association between creativity and the DMN subnetwork.

    更新日期:2019-12-23
  • Quercetin attenuates decrease of thioredoxin expression following focal cerebral ischemia and glutamate-induced neuronal cell damage
    Neuroscience (IF 3.244) Pub Date : 2019-12-23
    Dong-Ju Park; Ju-Bin Kang; Fawad-Ali Shah; Yeung-Bae Jin; Phil-Ok Koh

    Quercetin is a bioactive flavonoid which abundantly exists in vegetables and fruits. Quercetin exerts a neuroprotective effect against cerebral ischemia. Thioredoxin acts as antioxidant by regulating redox signaling. This study investigated whether quercetin regulates thioredoxin expression in focal cerebral ischemia and glutamate-induced neuronal cell death. Male Sprague Dawley rats (210-230 g) were intraperitoneally injected with vehicle or quercetin (10 mg/kg) 1 h prior to middle cerebral artery occlusion (MCAO). Cerebral cortex was collected 24 h after MCAO. MCAO led to neurological movement deficits, brain edema, and serious histopathological damages in cerebral cortex, and quercetin alleviated these damages following MCAO. We observed the change of thioredoxin expression in MCAO animals with quercetin using proteomic approach, reverse-transcription PCR, and Western blot analyses. Thioredoxin expression decreased in vehicle-treated MCAO animals, while quercetin attenuated this decrease. Moreover, quercetin treatment alleviated the decrease in the number of thioredoxin-positive cells in cerebral cortex of MCAO animals. Furthermore, immunoprecipitation analysis demonstrated that interaction of apoptosis signal-regulating kinase 1 (ASK1) and thioredoxin was decreased in MCAO animals with vehicle, while quercetin prevented MCAO-induced decrease in these binding. In addition, quercetin also alleviated the reduction of cell viability and the decrease in thioredoxin expression in glutamate-treated hippocampal cell line and primary cultures of cortical neurons. However in thioredoxin-silenced cortical neuron, anti-apoptotic effect of quercetin was decreased. Thus, changes of thioredoxin expression by quercetin may contribute to the neuroprotective effect of quercetin in focal cerebral ischemia. Our findings suggest that quercetin mediates its neuroprotective function by regulation of thioredoxin expression and maintenance of interaction between ASK1 and thioredoxin.

    更新日期:2019-12-23
  • Zinc modulates olfactory bulb kainate receptors
    Neuroscience (IF 3.244) Pub Date : 2019-12-23
    Laura J. Blakemore; Paul Q. Trombley

    Kainate receptors (KARs) are glutamate receptors with ionotropic and metabotropic activity composed of the GluK1-GluK5 subunits. We previously reported that KARs modulate excitatory and inhibitory transmission in the olfactory bulb (OB). Zinc, which is highly concentrated in the OB, also appears to modulate OB synaptic transmission via actions at other ionotropic glutamate receptors (i.e., AMPA, NMDA). However, few reports of effects of zinc on recombinant and/or native KARs exist and none have involved the OB. In the present study, we investigated the effects of exogenously applied zinc on OB KARs expressed by mitral/tufted (M/T) cells. We found that 100 µM zinc inhibits currents evoked by various combinations of KAR agonists (kainate or SYM 2081) and the AMPA receptor antagonist SYM 2206. The greatest degree of zinc-mediated inhibition was observed with coapplication of zinc with the GluK1- and GluK2- selective agonist SYM 2081 plus SYM 2206. This finding is consistent with prior reports of zinc’s inhibitory effects on some recombinant (homomeric GluK1 and GluK2 and heteromeric GluK2/GluK4 and GluK2/GluK5) KARs, although potentiation of other (GluK3, GluK2/3) KARs has also been described. It is also of potential importance given our previously reported molecular data suggesting that OB neurons express relatively high levels of GluK1 and GluK2. Our present findings suggest that a physiologically relevant concentration of zinc modulates KARs expressed by M/T cells. As M/T cells are targets of zinc-containing olfactory sensory neurons, synaptically released zinc may influence odor information-encoding synaptic circuits in the OB via actions at KARs.

    更新日期:2019-12-23
  • Aquaporin-4 dysregulation in a controlled cortical impact injury model of posttraumatic epilepsy
    Neuroscience (IF 3.244) Pub Date : 2019-12-19
    Jenny I. Szu; Som Chaturvedi; Dillon D. Patel; Devin K. Binder

    Posttraumatic epilepsy (PTE) is a long-term negative consequence of traumatic brain injury (TBI) in which recurrent spontaneous seizures occur after the initial head injury. PTE develops over an undefined period during which circuitry reorganization in the brain causes permanent hyperexcitability. The pathophysiology by which trauma leads to spontaneous seizures is unknown and clinically relevant models of PTE are key to understanding the molecular and cellular mechanisms underlying the development of PTE. In the present study, we used the controlled-cortical impact (CCI) injury model of TBI to induce PTE in mice and to characterize changes in aquaporin-4 (AQP4) expression. A moderate-severe TBI was induced in the right frontal cortex and video-electroencephalographic (vEEG) recordings were performed in the ipsilateral hippocampus to monitor for spontaneous seizures at 14, 30, 60, and 90 days post injury (dpi). The percentage of mice that developed PTE were 13%, 20%, 27%, and 14% at 14, 30, 60, and 90 dpi, respectively. We found a significant increase in AQP4 in the ipsilateral frontal cortex and hippocampus of mice that developed PTE compared to those that did not develop PTE. Interestingly, AQP4 was found to be mislocalized away from the perivascular endfeet and towards the neuropil in mice that developed PTE. Here, we report for the first time, AQP4 dysregulation in a model of PTE which may carry significant implications for epileptogenesis after TBI.

    更新日期:2019-12-20
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