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Differential contribution of canonical and noncanonical NLGN3 pathways to early social development and memory performance Mol. Brain (IF 3.6) Pub Date : 2024-03-12 Lin-Yu Li, Ayako Imai, Hironori Izumi, Ran Inoue, Yumie Koshidaka, Keizo Takao, Hisashi Mori, Tomoyuki Yoshida
Neuroligin (NLGN) 3 is a postsynaptic cell adhesion protein organizing synapse formation through two different types of transsynaptic interactions, canonical interaction with neurexins (NRXNs) and a recently identified noncanonical interaction with protein tyrosine phosphatase (PTP) δ. Although, NLGN3 gene is known as a risk gene for neurodevelopmental disorders such as autism spectrum disorder (ASD)
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Spermidine treatment: induction of autophagy but also apoptosis? Mol. Brain (IF 3.6) Pub Date : 2024-03-05 Maxinne Watchon, Amanda L. Wright, Holly I. Ahel, Katherine J. Robinson, Stuart K. Plenderleith, Andrea Kuriakose, Kristy C. Yuan, Angela S. Laird
Machado-Joseph disease (MJD), also known as spinocerebellar ataxia type 3, is a fatal neurodegenerative disease that causes loss of balance and motor co-ordination, eventually leading to paralysis. It is caused by the autosomal dominant inheritance of a long CAG trinucleotide repeat sequence within the ATXN3 gene, encoding for an expanded polyglutamine (polyQ) repeat sequence within the ataxin-3 protein
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Mutant α-synuclein causes death of human cortical neurons via ERK1/2 and JNK activation Mol. Brain (IF 3.6) Pub Date : 2024-03-05 Hidefumi Suzuki, Naohiro Egawa, Keiko Imamura, Takayuki Kondo, Takako Enami, Kayoko Tsukita, Mika Suga, Yuichiro Yada, Ran Shibukawa, Ryosuke Takahashi, Haruhisa Inoue
Synucleinopathies refer to a group of disorders characterized by SNCA/α-synuclein (α-Syn)-containing cytoplasmic inclusions and neuronal cell loss in the nervous system including the cortex, a common feature being cognitive impairment. Still, the molecular pathogenesis of cognitive decline remains poorly understood, hampering the development of effective treatments. Here, we generated induced pluripotent
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Crucial role of TFAP2B in the nervous system for regulating NREM sleep Mol. Brain (IF 3.6) Pub Date : 2024-02-27 Ayaka Nakai, Mitsuaki Kashiwagi, Tomoyuki Fujiyama, Kanako Iwasaki, Arisa Hirano, Hiromasa Funato, Masashi Yanagisawa, Takeshi Sakurai, Yu Hayashi
The AP-2 transcription factors are crucial for regulating sleep in both vertebrate and invertebrate animals. In mice, loss of function of the transcription factor AP-2β (TFAP2B) reduces non-rapid eye movement (NREM) sleep. When and where TFAP2B functions, however, is unclear. Here, we used the Cre-loxP system to generate mice in which Tfap2b was specifically deleted in the nervous system during development
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TREM2 improves microglia function and synaptic development in autism spectrum disorders by regulating P38 MAPK signaling pathway Mol. Brain (IF 3.6) Pub Date : 2024-02-26 Yi Tian, Xiao Xiao, Weiliang Liu, Shanqing Cheng, Na Qian, Ling Wang, Yang Liu, Rong Ai, Xiaoping Zhu
Autism spectrum disorder (ASD) encompasses a diverse range of neurodevelopmental disorders, but the precise underlying pathogenesis remains elusive. This study aim to explore the potential mechanism of TREM2 in regulating microglia function in ASD. The offspring rat model of ASD was established through prenatal exposure to valproic acid (VPA), and the behavioral symptoms of the ASD model were observed
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Selective enhancement of fear extinction by inhibiting neuronal adenylyl cyclase 1 (AC1) in aged mice Mol. Brain (IF 3.6) Pub Date : 2024-02-22 Wantong Shi, Qi-Yu Chen, Yujie Ma, Jinjin Wan, Xu-Hui Li, Min Zhuo
Adenylyl cyclase 1 (AC1) is a selective subtype of ACs, which is selectively expressed in neurons. The activation of AC1 is activity-dependent, and AC1 plays an important role in cortical excitation that contributes to chronic pain and related emotional disorders. Previous studies have reported that human-used NB001 (hNB001, a selective AC1 inhibitor) produced analgesic effects in different animal
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A simple and reliable method for claustrum localization across age in mice Mol. Brain (IF 3.6) Pub Date : 2024-02-17 Tarek Shaker, Gwyneth J. Dagpa, Vanessa Cattaud, Brian A. Marriott, Mariam Sultan, Mohammed Almokdad, Jesse Jackson
The anatomical organization of the rodent claustrum remains obscure due to lack of clear borders that distinguish it from neighboring forebrain structures. Defining what constitutes the claustrum is imperative for elucidating its functions. Methods based on gene/protein expression or transgenic mice have been used to spatially outline the claustrum but often report incomplete labeling and/or lack of
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In vitro modulation of mTOR and mGlur5 influence α-synuclein accumulation Mol. Brain (IF 3.6) Pub Date : 2024-02-15 Viktoria Xing, Kyle Biggar, Stephen S. G. Ferguson, Shawn Hayley
One of the main hallmarks of Parkinson’s disease (PD) is abnormal alpha-synuclein (α-syn) aggregation which forms the main component of intracellular Lewy body inclusions. This short report used preformed α-syn fibrils, as well as an A53T mutant α-syn adenovirus to mimic conditions of pathological protein aggregation in dopaminergic human derived SH-SY5Y neural cells. Since there is evidence that the
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Deleting IP6K1 stabilizes neuronal sodium–potassium pumps and suppresses excitability Mol. Brain (IF 3.6) Pub Date : 2024-02-13 Hongfu Jin, Aili Liu, Alfred C. Chin, Chenglai Fu, Hui Shen, Weiwei Cheng
Inositol pyrophosphates are key signaling molecules that regulate diverse neurobiological processes. We previously reported that the inositol pyrophosphate 5-InsP7, generated by inositol hexakisphosphate kinase 1 (IP6K1), governs the degradation of Na+/K+-ATPase (NKA) via an autoinhibitory domain of PI3K p85α. NKA is required for maintaining electrochemical gradients for proper neuronal firing. Here
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Single-molecule imaging of Tau reveals how phosphorylation affects its movement and confinement in living cells Mol. Brain (IF 3.6) Pub Date : 2024-02-12 Pranesh Padmanabhan, Andrew Kneynsberg, Esteban Cruz, Adam Briner, Jürgen Götz
Tau is a microtubule-associated protein that is regulated by post-translational modifications. The most studied of these modifications is phosphorylation, which affects Tau’s aggregation and loss- and gain-of-functions, including the interaction with microtubules, in Alzheimer’s disease and primary tauopathies. However, little is known about how Tau’s phosphorylation state affects its dynamics and
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Correction: The deficiency of Maged1 attenuates Parkinson’s disease progression in mice Mol. Brain (IF 3.6) Pub Date : 2024-02-09 Jie Wang, Sheng‑Ye Xu, Zhi‑Yuan Ye, Zhou‑Na Sun, Jia‑Qi Zhang, Cui Qi, Rui Liu, Xiang Gao, Chuan He, Wei‑Yan You, Jun Gao
Correction: Molecular Brain (2023) 16:22 https://doi.org/10.1186/s13041-023-01011-3 Following publication of the original article [1], the authors identified an error in Fig. 3a. The images of KO mice for Saline group in Fig. 3A were mistakenly assembled. The authors have carefully checked the raw data and identified that this was a case of clerical error. The correct figure and caption is given hereafter
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Outer layer of Vb neurons in medial entorhinal cortex project to hippocampal dentate gyrus in mice Mol. Brain (IF 3.6) Pub Date : 2024-02-05 Naoki Yamamoto, Jun Yokose, Kritika Ramesh, Takashi Kitamura, Sachie K. Ogawa
Entorhinal cortical (EC)-hippocampal (HPC) circuits are crucial for learning and memory. Although it was traditionally believed that superficial layers (II/III) of the EC mainly project to the HPC and deep layers (V/VI) receive input from the HPC, recent studies have highlighted the significant projections from layers Va and VI of the EC into the HPC. However, it still remains unknown whether Vb neurons
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The brain cytokine orchestra in multiple sclerosis: from neuroinflammation to synaptopathology Mol. Brain (IF 3.6) Pub Date : 2024-01-23 Roberta Amoriello, Christian Memo, Laura Ballerini, Clara Ballerini
The central nervous system (CNS) is finely protected by the blood–brain barrier (BBB). Immune soluble factors such as cytokines (CKs) are normally produced in the CNS, contributing to physiological immunosurveillance and homeostatic synaptic scaling. CKs are peptide, pleiotropic molecules involved in a broad range of cellular functions, with a pivotal role in resolving the inflammation and promoting
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Long-term inhibition of ODC1 in APP/PS1 mice rescues amyloid pathology and switches astrocytes from a reactive to active state Mol. Brain (IF 3.6) Pub Date : 2024-01-12 Mridula Bhalla, C. Justin Lee
Alzheimer’s disease (AD) is characterized by the loss of memory due to aggregation of misphosphorylated tau and amyloid beta (Aβ) plaques in the brain, elevated release of inhibitory neurotransmitter gamma-aminobutyric acid (GABA) and reactive oxygen species from astrocytes, and subsequent neurodegeneration. Recently, it was found that enzyme Ornithine Decarboxylase 1 (ODC1) acts as a bridge between
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Neurexin-1-dependent circuit activity is required for the maintenance of photoreceptor subtype identity in Drosophila Mol. Brain (IF 3.6) Pub Date : 2024-01-02 Gabrielle Lim-Kian-Siang, Arianna R. Izawa-Ishiguro, Yong Rao
In the human and Drosophila color vision system, each photoreceptor neuron (cone cell in humans and R7/R8 photoreceptor cell in Drosophila) makes a stochastic decision to express a single photopigment of the same family with the exclusion of the others. While recent studies have begun to reveal the mechanisms that specify the generation of cone subtypes during development in mammals, nothing is known
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Modulation of synaptic transmission through O-GlcNAcylation Mol. Brain (IF 3.6) Pub Date : 2024-01-02 Seunghyo Han, Jun-Nyeong Kim, Chan Ho Park, Jin-Seok Byun, Do-Yeon Kim, Hyoung-Gon Ko
O-GlcNAcylation is a posttranslational modification where N-acetylglucosamine (O-GlcNAc) is attached and detached from a serine/threonine position by two enzymes: O-GlcNAc transferase and O-GlcNAcase. In addition to roles in diabetes and cancer, recent pharmacological and genetic studies have revealed that O-GlcNAcylation is involved in neuronal function, specifically synaptic transmission. Global
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Exploring Piezo1, Piezo2, and TMEM150C in human brain tissues and their correlation with brain biomechanical characteristics Mol. Brain (IF 3.6) Pub Date : 2023-12-20 Arjun Raha, Yuning Wu, Lily Zhong, Jatheeshan Raveenthiran, Minji Hong, Aftab Taiyab, Li Wang, Bill Wang, Fei Geng
Unraveling the intricate relationship between mechanical factors and brain activity is a pivotal endeavor, yet the underlying mechanistic model of signaling pathways in brain mechanotransduction remains enigmatic. To bridge this gap, we introduced an in situ multi-scale platform, through which we delineate comprehensive brain biomechanical traits in white matter (WM), grey-white matter junctions (GW
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Pathophysiology of ion channels in amyotrophic lateral sclerosis Mol. Brain (IF 3.6) Pub Date : 2023-12-15 Robin N. Stringer, Norbert Weiss
Amyotrophic lateral sclerosis (ALS) stands as the most prevalent and severe form of motor neuron disease, affecting an estimated 2 in 100,000 individuals worldwide. It is characterized by the progressive loss of cortical, brainstem, and spinal motor neurons, ultimately resulting in muscle weakness and death. Although the etiology of ALS remains poorly understood in most cases, the remodelling of ion
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Role of spinal astrocytes through the perisynaptic astrocytic process in pathological pain Mol. Brain (IF 3.6) Pub Date : 2023-12-13 Hyoung-Gon Ko, Heejung Chun, Seunghyo Han, Bong-Kiun Kaang
Pathological pain is caused by abnormal activity in the neural circuit that transmits nociceptive stimuli. Beyond homeostatic functions, astrocytes actively participate in regulating synaptic transmission as members of tripartite synapses. The perisynaptic astrocytic process (PAP) is the key structure that allows astrocytes to play these roles and not only physically supports synapse formation through
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Attenuation of estrogen and its receptors in the post-menopausal stage exacerbates dyslipidemia and leads to cognitive impairment Mol. Brain (IF 3.6) Pub Date : 2023-11-20 Qinghai Meng, Ying Chao, Shurui Zhang, Xue Ding, Han Feng, Chenyan Zhang, Bowen Liu, Weijie Zhu, Yu Li, Qichun Zhang, Huangjin Tong, Lixing Wu, Huimin Bian
Cognitive dysfunction increases as menopause progresses. We previously found that estrogen receptors (ERs) contribute to dyslipidemia, but the specific relationship between ERs, dyslipidemia and cognitive dysfunction remains poorly understood. In the present study, we analyzed sequencing data from female hippocampus and normal breast aspirate samples from normal and Alzheimer’s disease (AD) women,
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Effects of MAP4K inhibition on neurite outgrowth Mol. Brain (IF 3.6) Pub Date : 2023-11-18 Di Ja Lasham, Reza K. Arta, Abdul Fuad Hadi, Jun Egawa, Vance P. Lemmon, Toshiyuki Takasugi, Michihiro Igarashi, Toshiyuki Someya
Protein kinases are responsible for protein phosphorylation and are involved in important intracellular signal transduction pathways in various cells, including neurons; however, a considerable number of poorly characterized kinases may be involved in neuronal development. Here, we considered mitogen-activated protein kinase kinase kinase kinases (MAP4Ks), related to as candidate regulators of neurite
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Optogenetic activation of dopamine D1 receptors in island cells of medial entorhinal cortex inhibits temporal association learning Mol. Brain (IF 3.6) Pub Date : 2023-11-14 Jun Yokose, Naoki Yamamoto, Sachie K. Ogawa, Takashi Kitamura
A critical feature of episodic memory formation is to associate temporally segregated events as an episode, called temporal association learning. The medial entorhinal cortical-hippocampal (EC-HPC) networks is essential for temporal association learning. We have previously demonstrated that pyramidal cells in the medial EC (MEC) layer III project to the hippocampal CA1 pyramidal cells and are necessary
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Impact of volume and expression time in an AAV-delivered channelrhodopsin Mol. Brain (IF 3.6) Pub Date : 2023-11-10 Sanaz Ansarifar, Gabija Andreikė, Milad Nazari, Rodrigo Labouriau, Sadegh Nabavi, Andrea Moreno
Optogenetics has revolutionised neuroscience research, but at the same time has brought a plethora of new variables to consider when designing an experiment with AAV-based targeted gene delivery. Some concerns have been raised regarding the impact of AAV injection volume and expression time in relation to longitudinal experimental designs. In this study, we investigated the efficiency of optically
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Chronic pregabalin treatment protects against spreading depolarization and alters hippocampal synaptic characteristics in a model of familial hemiplegic migraine-type 1 Mol. Brain (IF 3.6) Pub Date : 2023-11-03 Stuart M. Cain, Sascha R. A. Alles, Ray Gopaul, Louis-Philippe Bernier, Andrew C. Yung, Andrew Bauman, Yi Yang, Glen B. Baker, Piotr Kozlowski, Brian A. MacVicar, Terrance P. Snutch
Familial hemiplegic migraine type-1 (FHM-1) is a form of migraine with aura caused by mutations in the P/Q-type (Cav2.1) voltage-gated calcium channel. Pregabalin, used clinically in the treatment of chronic pain and epilepsy, inhibits P/Q-type calcium channel activity and recent studies suggest that it may have potential for the treatment of migraine. Spreading Depolarization (SD) is a neurophysiological
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Limitations of the human iPSC-derived neuron model for early-onset Alzheimer’s disease Mol. Brain (IF 3.6) Pub Date : 2023-11-03 Phoebe Valdes, Kenneth W. Henry, Michael Q. Fitzgerald, Koushik Muralidharan, Andrew B. Caldwell, Srinivasan Ramachandran, Lawrence S. B. Goldstein, William C. Mobley, Douglas R. Galasko, Shankar Subramaniam
Non-familial Alzheimer’s disease (AD) occurring before 65 years of age is commonly referred to as early-onset Alzheimer’s disease (EOAD) and constitutes ~ 5–6% of all AD cases (Mendez et al. in Continuum 25:34–51, 2019). While EOAD exhibits the same clinicopathological changes such as amyloid plaques, neurofibrillary tangles (NFTs), brain atrophy, and cognitive decline (Sirkis et al. in Mol Psychiatry
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MLKL regulates Cx43 ubiquitinational degradation and mediates neuronal necroptosis in ipsilateral thalamus after focal cortical infarction Mol. Brain (IF 3.6) Pub Date : 2023-10-30 Yanyan Tang, Quanhong Chu, Guanfeng Xie, Yafu Tan, Ziming Ye, Chao Qin
Necroptosis is known to play an important role in the pathophysiology of cerebral ischemia; however, its role in the occurrence of secondary thalamic injury after focal cerebral infarction and the mechanism about how mixed lineage kinase domain-like (MLKL) executes necroptosis in this pathophysiology are still unclear. In this study, Sprague-Dawley rats were subjected to distal branch of middle cerebral
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AAV-compatible optogenetic tools for activating endogenous calcium channels in vivo Mol. Brain (IF 3.6) Pub Date : 2023-10-17 Yeon Hee Kook, Hyoin Lee, Jinsu Lee, Yeonji Jeong, Jaerang Rho, Won Do Heo, Sangkyu Lee
Calcium ions (Ca2+) play pivotal roles in regulating diverse brain functions, including cognition, emotion, locomotion, and learning and memory. These functions are intricately regulated by a variety of Ca2+-dependent cellular processes, encompassing synaptic plasticity, neuro/gliotransmitter release, and gene expression. In our previous work, we developed ‘monster OptoSTIM1’ (monSTIM1), an improved
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α-Synuclein propagation leads to synaptic abnormalities in the cortex through microglial synapse phagocytosis Mol. Brain (IF 3.6) Pub Date : 2023-10-17 Dayana Pérez-Acuña, Soo Jean Shin, Ka Hyun Rhee, Sang Jeong Kim, Seung-Jae Lee
The major neuropathologic feature of Parkinson’s disease is the presence of widespread intracellular inclusions of α-synuclein known as Lewy bodies. Evidence suggests that these misfolded protein inclusions spread through the brain with disease progression. Changes in synaptic function precede neurodegeneration, and this extracellular α-synuclein can affect synaptic transmission. However, whether and
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Anterior cingulate cortex regulates pain catastrophizing-like behaviors in rats Mol. Brain (IF 3.6) Pub Date : 2023-10-13 Hyun Jung Jee, Elaine Zhu, Mengqi Sun, Weizhuo Liu, Qiaosheng Zhang, Jing Wang
Negative pain expectation including pain catastrophizing is a well-known clinical phenomenon whereby patients amplify the aversive value of a painful or oftentimes even a similar, non-painful stimulus. Mechanisms of pain catastrophizing, however, remain elusive. Here, we modeled pain catastrophizing behavior in rats, and found that rats subjected to repeated noxious pin pricks on one paw demonstrated
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Rab11a in the spinal cord: an essential contributor to complete Freund’s adjuvant-induced inflammatory pain in mice Mol. Brain (IF 3.6) Pub Date : 2023-09-28 Jun-Xiang Gu, Jian Wang, Fu-Juan Ma, Miao-Miao Liu, Si-Hai Chen, Yi Wei, Yi-Fan Xiao, Pei-Yuan Lv, Xin Liu, Jian-Qiang Qu, Xian-Xia Yan, Tao Chen
Inflammatory pain is a commonly observed clinical symptom in a range of acute and chronic diseases. However, the mechanism of inflammatory pain is far from clear yet. Rab11a, a small molecule guanosine triphosphate enzyme, is reported to regulate orofacial inflammatory pain in our previous works. However, the mechanism of Rab11a’s involvement in the regulation of inflammatory pain remains obscure.
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Novelty-induced memory consolidation is accompanied by increased Agap3 transcription: a cross-species study Mol. Brain (IF 3.6) Pub Date : 2023-09-25 Kristoffer Højgaard, Bianka Szöllősi, Kim Henningsen, Natsumi Minami, Nobuhiro Nakanishi, Erik Kaadt, Makoto Tamura, Richard G.M. Morris, Tomonori Takeuchi, Betina Elfving
Novelty-induced memory consolidation is a well-established phenomenon that depends on the activation of a locus coeruleus-hippocampal circuit. It is associated with the expression of activity-dependent genes that may mediate initial or cellular memory consolidation. Several genes have been identified to date, however, to fully understand the mechanisms of memory consolidation, additional candidates
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Electrophysiological characterization of a Cav3.2 calcium channel missense variant associated with epilepsy and hearing loss Mol. Brain (IF 3.6) Pub Date : 2023-09-21 Robin N. Stringer, Leos Cmarko, Gerald W. Zamponi, Michel De Waard, Norbert Weiss
T-type calcium channelopathies encompass a group of human disorders either caused or exacerbated by mutations in the genes encoding different T-type calcium channels. Recently, a new heterozygous missense mutation in the CACNA1H gene that encodes the Cav3.2 T-type calcium channel was reported in a patient presenting with epilepsy and hearing loss—apparently the first CACNA1H mutation to be associated
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Comparison of Huntington’s disease phenotype progression in male and female heterozygous FDNQ175 mice Mol. Brain (IF 3.6) Pub Date : 2023-09-19 Si Han Li, Tash-Lynn L. Colson, Jingwei Chen, Khaled S. Abd-Elrahman, Stephen S. G. Ferguson
Huntington’s Disease (HD) is an inherited autosomal dominant neurodegenerative disorder that leads to progressive motor and cognitive impairment due to the expansion of a polyglutamine (CAG) repeat in the N-terminal region of the huntingtin (Htt) protein. The creation of HD mouse models represents a critical step in the research for HD treatment. Among the currently available HD mouse models, the zQ175
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Recombinase-independent AAV for anterograde transsynaptic tracing Mol. Brain (IF 3.6) Pub Date : 2023-09-15 Islam Faress, Valentina Khalil, Haruka Yamamoto, Szilard Sajgo, Keisuke Yonehara, Sadegh Nabavi
Viral transsynaptic labeling has become indispensable for investigating the functional connectivity of neural circuits in the mammalian brain. Adeno-associated virus serotype 1 (AAV1) allows for anterograde transneuronal labeling and manipulation of postsynaptic neurons. However, it is limited to delivering an AAV1 expressing a recombinase which relies on using transgenic animals or genetic access
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Changes in oligodendroglial subpopulations in Parkinson’s disease Mol. Brain (IF 3.6) Pub Date : 2023-09-14 Eun-Jin Bae, Dayana Pérez-Acuña, Ka Hyun Rhee, Seung-Jae Lee
Parkinson’s disease (PD) is characterized by a selective loss of dopaminergic neurons. While most research on PD conducted to date has focused on neurons and, to a certain extent, glia, few studies have investigated changes in oligodendroglia. Here, we investigated the heterogeneity of oligodendrocytes from PD patients compared with those of control cases by analyzing single-nuclei transcriptomes.
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Inhibitory insula-ACC projections modulate affective but not sensory aspects of neuropathic pain Mol. Brain (IF 3.6) Pub Date : 2023-08-21 Heloísa Alonso-Matielo, Zizhen Zhang, Eder Gambeta, Junting Huang, Lina Chen, Gabriel Oliveira de Melo, Camila Squarzoni Dale, Gerald W. Zamponi
The insula and anterior cingulate cortex (ACC) are brain regions that undergo structural and functional reorganization in neuropathic pain states. Here, we aimed to study inhibitory parvalbumin positive (PV+) posterior insula (pIC) to posterior ACC (pACC) projections, and to evaluate the effects of direct optogenetic manipulation of such projections on mechanical nociception and spontaneous ongoing
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Profiling tyrosine kinase inhibitors as AD therapeutics in a mouse model of AD Mol. Brain (IF 3.6) Pub Date : 2023-08-14 Hyun-ju Lee, Jeong-Woo Hwang, Jin-Hee Park, Yoo Joo Jeong, Ji-Yeong Jang, Hyang-Sook Hoe
Alzheimer’s disease (AD) is a neurodegenerative disease characterized by Aβ deposition, tauopathy, neuroinflammation, and impaired cognition. The recent identification of associations between protein kinases and AD pathology has spurred interest in tyrosine kinase inhibitors (TKIs) as potential strategic therapeutic agents for AD. In the present study, we investigated whether the TKIs ibrutinib, PD180970
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Specific vulnerability of iPSC-derived motor neurons with TDP-43 gene mutation to oxidative stress Mol. Brain (IF 3.6) Pub Date : 2023-07-26 Asako Onda-Ohto, Minami Hasegawa-Ogawa, Hiromasa Matsuno, Tomotaka Shiraishi, Keiko Bono, Hiromi Hiraki, Yumi Kanegae, Yasuyuki Iguchi, Hirotaka James Okano
Amyotrophic lateral sclerosis (ALS) is a disease that affects motor neurons and has a poor prognosis. We focused on TAR DNA-binding protein 43 kDa (TDP-43), which is a common component of neuronal inclusions in many ALS patients. To analyze the contribution of TDP-43 mutations to ALS in human cells, we first introduced TDP-43 mutations into healthy human iPSCs using CRISPR/Cas9 gene editing technology
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C1ql1-Bai3 signaling is necessary for climbing fiber synapse formation in mature Purkinje cells in coordination with neuronal activity Mol. Brain (IF 3.6) Pub Date : 2023-07-24 Takahiro Aimi, Keiko Matsuda, Michisuke Yuzaki
Changes in neural activity induced by learning and novel environments have been reported to lead to the formation of new synapses in the adult brain. However, the underlying molecular mechanism is not well understood. Here, we show that Purkinje cells (PCs), which have established adult-type monosynaptic innervation by climbing fibers (CFs) after elimination of weak CFs during development, can be reinnervated
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Antihyperalgesic effect of joint mobilization requires Cav3.2 calcium channels Mol. Brain (IF 3.6) Pub Date : 2023-07-18 Daniel F. Martins, Victor Sorrentino, Leidiane Mazzardo-Martins, William R. Reed, Adair R. S. Santos, Vinícius M. Gadotti, Gerald W. Zamponi
The present study was undertaken to explore the relative contributions of Cav3.2 T-type channels to mediating the antihyperalgesic activity of joint manipulation (JM) therapy. We used the chronic constriction injury model (CCI) to induce peripheral neuropathy and chronic pain in male mice, followed by JM. We demonstrate that JM produces long-lasting mechanical anti-hyperalgesia that is abolished in
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Ameliorative effects of Fingolimod (FTY720) on microglial activation and psychosis-related behavior in short term cuprizone exposed mice Mol. Brain (IF 3.6) Pub Date : 2023-07-12 Siyao Li, Koki Sakurai, Masahiro Ohgidani, Takahiro A. Kato, Takatoshi Hikida
Schizophrenia is a psychiatric disorder that affects around 1% of the population in widespread populations, with severe cases leading to long-term hospitalization and necessitation of lifelong treatment. Recent studies on schizophrenia have highlighted the involvement of inflammatory and immunoregulatory mechanisms with the onset of symptoms, and the usage of anti-inflammatory treatments are being
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Dynamic alteration of intrinsic properties of the cerebellar Purkinje cell during the motor memory consolidation Mol. Brain (IF 3.6) Pub Date : 2023-07-10 Dong Cheol Jang, Geehoon Chung, Sun Kwang Kim, Sang Jeong Kim
Intrinsic plasticity of the cerebellar Purkinje cell (PC) plays a critical role in motor memory consolidation. However, detailed changes in their intrinsic properties during memory consolidation are not well understood. Here, we report alterations in various properties involved in intrinsic excitability, such as the action potential (AP) threshold, AP width, afterhyperpolarization (AHP), and sag voltage
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Reactive astrocytes mediate TSPO overexpression in response to sustained CNTF exposure in the rat striatum Mol. Brain (IF 3.6) Pub Date : 2023-07-05 Kelly Ceyzériat, Alekos Nicolaides, Quentin Amossé, Christine Fossey, Thomas Cailly, Frédéric Fabis, Valentina Garibotto, Carole Escartin, Benjamin B. Tournier, Philippe Millet
The 18 kDa translocator protein (TSPO) is a classical marker of neuroinflammation targeted for in vivo molecular imaging. Microglial cells were originally thought to be the only source of TSPO overexpression but astrocytes, neurons and endothelial cells can also up-regulate TSPO depending on the pathological context. This study aims to determine the cellular origin of TSPO overexpression in a simplified
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Optogenetic dissection of RET signaling reveals robust activation of ERK and enhanced filopodia-like protrusions of regenerating axons Mol. Brain (IF 3.6) Pub Date : 2023-07-04 Bobae Hyeon, Heeyoung Lee, Nury Kim, Won Do Heo
RET (REarranged during Transfection) is a receptor tyrosine kinase that transduces various external stimuli into biological functions, such as survival and differentiation, in neurons. In the current study, we developed an optogenetic tool for modulating RET signaling, termed optoRET, combining the cytosolic region of human RET with a blue-light–inducible homo-oligomerizing protein. By varying the
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mTORC1-mediated acquisition of reward-related representations by hippocampal somatostatin interneurons Mol. Brain (IF 3.6) Pub Date : 2023-07-03 François-Xavier Michon, Isabel Laplante, Anthony Bosson, Richard Robitaille, Jean-Claude Lacaille
Plasticity of principal cells and inhibitory interneurons underlies hippocampal memory. Bidirectional modulation of somatostatin cell mTORC1 activity, a crucial translational control mechanism in synaptic plasticity, causes parallel changes in hippocampal CA1 somatostatin interneuron (SOM-IN) long-term potentiation and hippocampus-dependent memory, indicating a key role in learning. However, SOM-IN
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The lateral habenula nucleus regulates pruritic sensation and emotion Mol. Brain (IF 3.6) Pub Date : 2023-06-27 Rui Chen, Xiang Xu, Xin-Yue Wang, Wen-Bin Jia, De-Shan Zhao, Na Liu, Zhen Pang, Xiao-Qing Liu, Yan Zhang
Itch is a complex aversive sensory and emotional experience. As a most upsetting symptom in many dermatological and systemic diseases, it lacks efficient treatments. The lateral habenula nucleus (LHb) encodes negative emotions in the epithalamus and has been implicated in pain and analgesia. Nevertheless, the role of the lateral habenula nucleus in the pruritic sensation and emotion remains elusive
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BCAT1 controls embryonic neural stem cells proliferation and differentiation in the upper layer neurons Mol. Brain (IF 3.6) Pub Date : 2023-06-21 Shukui Zhang, Jinyue Zhao, Cheng Zhao, Libo Su, Jianwei Jiao
The regulation of neural stem cell (NSC) proliferation and differentiation during brain development is a precisely controlled process, with the production of different neuronal subtypes governed by strict timelines. Glutamate is predominantly used as a neurotransmitter by the subtypes of neurons in the various layers of the cerebral cortex. The expression pattern of BCAT1, a gene involved in glutamate
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Activation of angiotensin-converting enzyme 2 produces an antidepressant-like effect via MAS receptors in mice Mol. Brain (IF 3.6) Pub Date : 2023-06-13 Osamu Nakagawasai, Kohei Takahashi, Taisei Koyama, Ryota Yamagata, Wataru Nemoto, Koichi Tan-No
Angiotensin (Ang)-converting-enzyme (ACE) 2 converts Ang II into Ang (1–7), which in turn acts on MAS receptors (ACE2/Ang (1–7)/MAS receptors pathway). This pathway has neuroprotective properties, making it a potential therapeutic target for psychiatric disorders such as depression. Thus, we examined the effects of diminazene aceturate (DIZE), an ACE2 activator, on depressive-like behavior using behavioral
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Loosely synchronized activation of anterior cingulate cortical neurons for scratching response during histamine-induced itch Mol. Brain (IF 3.6) Pub Date : 2023-06-13 Chiwoo Lee, Jihae Oh, Jae-Hyung Lee, Bong-Kiun Kaang, Hyoung-Gon Ko
Itch is a distinctive sensation that causes a specific affection and scratching reaction. The anterior cingulate cortex (ACC) has been linked to itch sensation in numerous studies; however, its precise function in processing pruritic inputs remains unknown. Distinguishing the precise role of the ACC in itch sensation can be challenging because of its capacity to conduct heterologous neurophysiological
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A new AAV tool for highly preferentially targeting hippocampal CA2 Mol. Brain (IF 3.6) Pub Date : 2023-06-11 Siqi Peng, Wenzhen Gu, Wenxiu Zhu, Yan Zhuang, Xiuqi Yang, Yaochen Lv, Sibie Meng, Wei Xie, Moyi Li
Mice hippocampus contains three prominent subregions, CA1, CA3 and DG and is well regarded as an essential multiple task processor for learning, memory and cognition based on tremendous studies on these three subregions. The narrow region sandwiched between CA1 and CA3 called CA2 has been neglected for a long time. But it raises great attentions recently since this region manifests the indispensable
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Regulation of dendritic spine length in corticopontine layer V pyramidal neurons by autism risk gene β3 integrin Mol. Brain (IF 3.6) Pub Date : 2023-06-09 Lucia Celora, Fanny Jaudon, Carmela Vitale, Lorenzo A. Cingolani
The relationship between autism spectrum disorder (ASD) and dendritic spine abnormalities is well known, but it is unclear whether the deficits relate to specific neuron types and brain regions most relevant to ASD. Recent genetic studies have identified a convergence of ASD risk genes in deep layer pyramidal neurons of the prefrontal cortex. Here, we use retrograde recombinant adeno-associated viruses
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Partial inactivation of songbird auditory cortex impairs both tempo and pitch discrimination Mol. Brain (IF 3.6) Pub Date : 2023-06-03 Gunsoo Kim, Miguel Sánchez-Valpuesta, Mimi H. Kao
Neuronal tuning for spectral and temporal features has been studied extensively in the auditory system. In the auditory cortex, diverse combinations of spectral and temporal tuning have been found, but how specific feature tuning contributes to the perception of complex sounds remains unclear. Neurons in the avian auditory cortex are spatially organized in terms of spectral or temporal tuning widths
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Analgesia by intrathecal delta-9-tetrahydrocannabinol is dependent on Cav3.2 calcium channels Mol. Brain (IF 3.6) Pub Date : 2023-05-25 Vinicius de Maria Gadotti, Flavia Tasmin Techera Antunes, Gerald W. Zamponi
Delta-9-tetrahydrocannabinol (Δ9-THC) is known to produce systemic analgesia that involves CB1 and CB2 cannabinoid receptors. However, there is compelling evidence that Δ9-THC can potently inhibit Cav3.2T-type calcium channels which are highly expressed in dorsal root ganglion neurons and in the dorsal horn of the spinal cord. Here, we investigated whether spinal analgesia produced by Δ9-THC involves
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Maturation of nucleus accumbens synaptic transmission signals a critical period for the rescue of social deficits in a mouse model of autism spectrum disorder Mol. Brain (IF 3.6) Pub Date : 2023-05-24 Melina Matthiesen, Abdessattar Khlaifia, Carl Frank David Steininger, Maryam Dadabhoy, Unza Mumtaz, Maithe Arruda-Carvalho
Social behavior emerges early in development, a time marked by the onset of neurodevelopmental disorders featuring social deficits, including autism spectrum disorder (ASD). Although social deficits are at the core of the clinical diagnosis of ASD, very little is known about their neural correlates at the time of clinical onset. The nucleus accumbens (NAc), a brain region extensively implicated in
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Burst firing is required for induction of Hebbian LTP at lateral perforant path to hippocampal granule cell synapses Mol. Brain (IF 3.6) Pub Date : 2023-05-22 Yoonsub Kim, Sooyun Kim, Won-Kyung Ho, Suk-Ho Lee
High frequency burst firing is critical in summation of back-propagating action potentials (APs) in dendrites, which may greatly depolarize dendritic membrane potential. The physiological significance of burst firings of hippocampal dentate GCs in synaptic plasticity remains unknown. We found that GCs with low input resistance could be categorized into regular-spiking (RS) and burst-spiking (BS) cells
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Comprehensive behavioral analyses of mice with a glycine receptor alpha 4 deficiency Mol. Brain (IF 3.6) Pub Date : 2023-05-22 Mohamed Darwish, Satoko Hattori, Hirofumi Nishizono, Tsuyoshi Miyakawa, Nozomu Yachie, Keizo Takao
Glycine receptors (GlyRs) are ligand-gated chloride channels comprising alpha (α1–4) and β subunits. The GlyR subunits play major roles in the mammalian central nervous system, ranging from regulating simple sensory information to modulating higher-order brain function. Unlike the other GlyR subunits, GlyR α4 receives relatively little attention because the human ortholog lacks a transmembrane domain
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Interneuronal GluK1 kainate receptors control maturation of GABAergic transmission and network synchrony in the hippocampus Mol. Brain (IF 3.6) Pub Date : 2023-05-20 Simo Ojanen, Tatiana Kuznetsova, Zoia Kharybina, Vootele Voikar, Sari E. Lauri, Tomi Taira
Kainate type glutamate receptors (KARs) are strongly expressed in GABAergic interneurons and have the capability of modulating their functions via ionotropic and G-protein coupled mechanisms. GABAergic interneurons are critical for generation of coordinated network activity in both neonatal and adult brain, yet the role of interneuronal KARs in network synchronization remains unclear. Here, we show
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Ankyrin2 is essential for neuronal morphogenesis and long-term courtship memory in Drosophila Mol. Brain (IF 3.6) Pub Date : 2023-05-16 Silvia Schwartz, Sarah J Wilson, Tracy K Hale, Helen L Fitzsimons
Dysregulation of HDAC4 expression and/or nucleocytoplasmic shuttling results in impaired neuronal morphogenesis and long-term memory in Drosophila melanogaster. A recent genetic screen for genes that interact in the same molecular pathway as HDAC4 identified the cytoskeletal adapter Ankyrin2 (Ank2). Here we sought to investigate the role of Ank2 in neuronal morphogenesis, learning and memory. We found
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Enhanced primary ciliogenesis via mitochondrial oxidative stress activates AKT to prevent neurotoxicity in HSPA9/mortalin-depleted SH-SY5Y cells Mol. Brain (IF 3.6) Pub Date : 2023-05-11 Ji-Eun Bae, Soyoung Jang, Joon Bum Kim, Hyejin Hyung, Na Yeon Park, Yong Hwan Kim, So Hyun Kim, Seong Hyun Kim, Jin Min Ha, Gyeong Seok Oh, Kyuhee Park, Kwiwan Jeong, Jae Seon Jang, Doo Sin Jo, Pansoo Kim, Hyun-Shik Lee, Zae Young Ryoo, Dong-Hyung Cho
The primary cilium, an antenna-like structure on the cell surface, acts as a mechanical and chemical sensory organelle. Primary cilia play critical roles in sensing the extracellular environment to coordinate various developmental and homeostatic signaling pathways. Here, we showed that the depletion of heat shock protein family A member 9 (HSPA9)/mortalin stimulates primary ciliogenesis in SH-SY5Y
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A new paradigm of learned cooperation reveals extensive social coordination and specific cortical activation in mice Mol. Brain (IF 3.6) Pub Date : 2023-05-11 Ke-Ming Zhang, Yan Shen, Chun-Hui Jia, Hao Wang, Guo-Qiang Bi, Pak-Ming Lau
Cooperation is a social behavior crucial for the survival of many species, including humans. Several experimental paradigms have been established to study cooperative behavior and related neural activity in different animal species. Although mice exhibit limited cooperative capacity in some behavioral paradigms, it is still interesting to explore their cooperative behavior and the underlying neural