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The role of pruriceptors in enhancing sensitivity to pruritogens in a murine chronic compression model of dorsal root ganglion Mol. Brain (IF 4.686) Pub Date : 2021-01-19 Tao Wang; Jin Tao; Yehong Fang; Chao Ma
Chronic pruritus is a symptom that commonly observed in neurological diseases. It has been hypothesized that the chronic pruritus may result from sensitization of itch-signaling pathways but the mechanisms remain obscure. In this study, we established a mouse model of chronic compression of dorsal root ganglion (CCD) and injected various pruritogenic and algogenic agents intradermally to the calf skin
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Schizophrenia-associated dysbindin modulates axonal mitochondrial movement in cooperation with p150glued Mol. Brain (IF 4.686) Pub Date : 2021-01-18 Bo Kyoung Suh; Seol-Ae Lee; Cana Park; Yeongjun Suh; Soo Jeong Kim; Youngsik Woo; Truong Thi My Nhung; Su Been Lee; Dong Jin Mun; Bon Seong Goo; Hyun Sun Choi; So Jung Kim; Sang Ki Park
Mitochondrial movement in neurons is finely regulated to meet the local demand for energy and calcium buffering. Elaborate transport machinery including motor complexes is required to deliver and localize mitochondria to appropriate positions. Defects in mitochondrial transport are associated with various neurological disorders without a detailed mechanistic information. In this study, we present evidence
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Choice-dependent cross-modal interaction in the medial prefrontal cortex of rats Mol. Brain (IF 4.686) Pub Date : 2021-01-15 Mengyao Zheng; Jinghong Xu; Les Keniston; Jing Wu; Song Chang; Liping Yu
Cross-modal interaction (CMI) could significantly influence the perceptional or decision-making process in many circumstances. However, it remains poorly understood what integrative strategies are employed by the brain to deal with different task contexts. To explore it, we examined neural activities of the medial prefrontal cortex (mPFC) of rats performing cue-guided two-alternative forced-choice
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Schizophrenia risk ZNF804A interacts with its associated proteins to modulate dendritic morphology and synaptic development Mol. Brain (IF 4.686) Pub Date : 2021-01-14 Fengping Dong; Joseph Mao; Miranda Chen; Joy Yoon; Yingwei Mao
Schizophrenia (SZ) is a devastating brain disease that affects about 1% of world population. Among the top genetic associations, zinc finger protein 804A (ZNF804A) gene encodes a zinc finger protein, associated with SZ and biolar disorder (BD). Copy number variants (CNVs) of ZNF804A have been observed in patients with autism spectrum disorders (ASDs), anxiety disorder, and BD, suggesting that ZNF804A
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Interleukin-17 induced by cumulative mild stress promoted depression-like behaviors in young adult mice Mol. Brain (IF 4.686) Pub Date : 2021-01-13 Jinho Kim; Yoo-Hun Suh; Keun-A Chang
The number of young adult patients with major depression, one of the most common mental disorders, is gradually increasing in modern society. Stressful experiences in early life are considered one of the risk factors for chronic depressive symptoms, along with an abnormal inflammatory response in later life. Although increased inflammatory activity has been identified in patients with depression, the
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Distinct role of 5′UTR sequences in dendritic trafficking of BDNF mRNA: additional mechanisms for the BDNF splice variants spatial code Mol. Brain (IF 4.686) Pub Date : 2021-01-12 Andrea Colliva; Enrico Tongiorgi
The neurotrophin Brain-derived neurotrophic factor (BDNF) is encoded by multiple bipartite transcripts. Each BDNF transcript is composed by one out of 11 alternatively spliced exons containing the 5′untranslated region (UTR), and one common exon encompassing the coding sequence (CDS) and the 3′UTR with two variants (short and long). In neurons, BDNF mRNA variants have a distinct subcellular distribution
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The nuclear lamina is a hub for the nuclear function of Jacob Mol. Brain (IF 4.686) Pub Date : 2021-01-12 Sebastian Samer; Rajeev Raman; Gregor Laube; Michael R. Kreutz; Anna Karpova
Jacob is a synapto-nuclear messenger protein that couples NMDAR activity to CREB-dependent gene expression. In this study, we investigated the nuclear distribution of Jacob and report a prominent targeting to the nuclear envelope that requires NMDAR activity and nuclear import. Immunogold electron microscopy and proximity ligation assay combined with STED imaging revealed preferential association of
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Roles of palmitoylation in structural long-term synaptic plasticity Mol. Brain (IF 4.686) Pub Date : 2021-01-11 Benjun Ji; Małgorzata Skup
Long-term potentiation (LTP) and long-term depression (LTD) are important cellular mechanisms underlying learning and memory processes. N-Methyl-d-aspartate receptor (NMDAR)-dependent LTP and LTD play especially crucial roles in these functions, and their expression depends on changes in the number and single channel conductance of the major ionotropic glutamate receptor α-amino-3-hydroxy-5-methyl
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Regulation of behavioral response to stress by microRNA-690 Mol. Brain (IF 4.686) Pub Date : 2021-01-09 Jungyoung Park; Joonhee Lee; Koeul Choi; Hyo Jung Kang
Psychiatric disorders are affected by genetic susceptibility and environmental adversities. Therefore, the regulation of gene expression under certain environments, such as stress, is a key issue in psychiatric disorders. MicroRNAs (miRNAs) have been implicated as post-transcriptional regulators of several biological processes, which can be differentially controlled through the targeting of multiple
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Increased O-GlcNAcylation of Drp1 by amyloid-beta promotes mitochondrial fission and dysfunction in neuronal cells Mol. Brain (IF 4.686) Pub Date : 2021-01-09 So Jung Park; Ji-Eun Bae; Doo Sin Jo; Joon Bum Kim; Na Yeon Park; Jianguo Fang; Yong-Keun Jung; Dong Gyu Jo; Dong-Hyung Cho
As a dynamic organelle, mitochondria continuously fuse and divide with adjacent mitochondria. Imbalance in mitochondria dynamics leads to their dysfunction, which implicated in neurodegenerative diseases. However, how mitochondria alteration and glucose defect contribute to pathogenesis of Alzheimer’s disease (AD) is still largely unknown. Dynamin‐related protein 1 (Drp1) is an essential regulator
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Global knockdown of glutamate decarboxylase 67 elicits emotional abnormality in mice Mol. Brain (IF 4.686) Pub Date : 2021-01-07 Shigeo Miyata; Toshikazu Kakizaki; Kazuyuki Fujihara; Hideru Obinata; Touko Hirano; Junichi Nakai; Mika Tanaka; Shigeyoshi Itohara; Masahiko Watanabe; Kenji F. Tanaka; Manabu Abe; Kenji Sakimura; Yuchio Yanagawa
Reduced expression of glutamate decarboxylase 67 (GAD67), encoded by the Gad1 gene, is a consistent finding in postmortem brains of patients with several psychiatric disorders, including schizophrenia, bipolar disorder and major depressive disorder. The dysfunction of GAD67 in the brain is implicated in the pathophysiology of these psychiatric disorders; however, the neurobiological consequences of
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A CACNA1A variant associated with trigeminal neuralgia alters the gating of Cav2.1 channels Mol. Brain (IF 4.686) Pub Date : 2021-01-07 Eder Gambeta; Maria A. Gandini; Ivana A. Souza; Laurent Ferron; Gerald W. Zamponi
A novel missense mutation in the CACNA1A gene that encodes the pore forming α1 subunit of the CaV2.1 voltage-gated calcium channel was identified in a patient with trigeminal neuralgia. This mutation leads to a substitution of proline 2455 by histidine (P2455H) in the distal C-terminus region of the channel. Due to the well characterized role of this channel in neurotransmitter release, our aim was
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Evaluating the genetic effects of sex hormone traits on the development of mental traits: a polygenic score analysis and gene-environment-wide interaction study in UK Biobank cohort Mol. Brain (IF 4.686) Pub Date : 2021-01-06 Xiao Liang; ShiQiang Cheng; Jing Ye; XiaoMeng Chu; Yan Wen; Li Liu; Xin Qi; YuMeng Jia; Feng Zhang
To evaluate the genetic effects of sex hormone traits on the development of mental traits in middle-aged adults. The SNPs associated with sex hormone traits were derived from a two-stage genome-wide association study (GWAS). Four sex hormone traits were selected in the current study, including sex hormone-binding globulin (SHBG), testosterone, bioavailable testosterone and estradiol. The polygenic
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Optogenetic inhibition of medial entorhinal cortex inputs to the hippocampus during a short period of time right after learning disrupts contextual fear memory formation Mol. Brain (IF 4.686) Pub Date : 2021-01-06 Min Soo Kang; Jin-Hee Han
Formation of temporal association memory and context-specific fear memory is thought to require medial entorhinal cortex (MEC) inputs to the hippocampus during learning events. However, whether the MEC inputs are also involved in memory formation during a post-learning period has not been directly tested yet. To examine this possibility, we optogenetically inhibited axons and terminals originating
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Conditional knock out of transcription factor CTCF in excitatory neurons induces cognitive deficiency Mol. Brain (IF 4.686) Pub Date : 2021-01-05 Dong Il Choi; Myeongwon Kim; Somi Kim; Nam-Kyung Yu; Chuljung Kwak; Hyunhyo Seo; Kyungmin Lee; Bong-Kiun Kaang
CCCTC-binding factor (CTCF) is a transcription factor that is involved in organizing chromatin structure. A reduction of CTCF expression is known to develop distinct clinical features. Furthermore, conditional knock out (cKO) study revealed reactive gliosis of astrocytes and microglia followed by age-dependent cell death in the excitatory neurons of CTCF cKO mice. To assess the cognitive ability in
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Identification of FMRP target mRNAs in the developmental brain: FMRP might coordinate Ras/MAPK, Wnt/β-catenin, and mTOR signaling during corticogenesis Mol. Brain (IF 4.686) Pub Date : 2020-12-16 Cristine R. Casingal; Takako Kikkawa; Hitoshi Inada; Yukio Sasaki; Noriko Osumi
Corticogenesis is one of the most critical and complicated processes during embryonic brain development. Any slight impairment in corticogenesis could cause neurodevelopmental disorders such as Fragile X syndrome (FXS), of which symptoms contain intellectual disability (ID) and autism spectrum disorder (ASD). Fragile X mental retardation protein (FMRP), an RNA-binding protein responsible for FXS, shows
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Prefrontal cortex, dorsomedial striatum, and dentate gyrus are necessary in the object-based attention test in mice Mol. Brain (IF 4.686) Pub Date : 2020-12-14 Bolati Wulaer; Kazuo Kunisawa; Hisayoshi Kubota; Willy Jaya Suento; Kuniaki Saito; Akihiro Mouri; Toshitaka Nabeshima
Disturbances of attention are a common behavioral feature associated with neuropsychiatric disorders with largely unknown underlying causes. We previously developed an object-based attention test (OBAT) as a simple and practical method for evaluating attention in mice. Since its establishment, the test has become a popular method for assessing attention and related underlying mechanisms in various
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Overexpression of astroglial major histocompatibility complex class I in the medial prefrontal cortex impairs visual discrimination learning in mice Mol. Brain (IF 4.686) Pub Date : 2020-12-14 Bolati Wulaer; Kazuhiro Hada; Akira Sobue; Norimichi Itoh; Toshitaka Nabeshima; Taku Nagai; Kiyofumi Yamada
Immune molecules, such as cytokines, complement, and major histocompatibility complex (MHC) proteins, in the central nervous system are often associated with neuropsychiatric disorders. Neuronal MHC class I (MHCI), such as H-2D, regulate neurite outgrowth, the establishment and function of cortical connections, and activity-dependent refinement in mice. We previously established mice expressing MHCI
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Altered cleavage plane orientation with increased genomic aneuploidy produced by receptor-mediated lysophosphatidic acid (LPA) signaling in mouse cerebral cortical neural progenitor cells Mol. Brain (IF 4.686) Pub Date : 2020-12-14 Whitney S. McDonald; Kyoko Miyamoto; Richard Rivera; Grace Kennedy; Beatriz S. V. Almeida; Marcy A. Kingsbury; Jerold Chun
The brain is composed of cells having distinct genomic DNA sequences that arise post-zygotically, known as somatic genomic mosaicism (SGM). One form of SGM is aneuploidy—the gain and/or loss of chromosomes—which is associated with mitotic spindle defects. The mitotic spindle orientation determines cleavage plane positioning and, therefore, neural progenitor cell (NPC) fate during cerebral cortical
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Integrin β3 organizes dendritic complexity of cerebral cortical pyramidal neurons along a tangential gradient Mol. Brain (IF 4.686) Pub Date : 2020-12-14 Brian D. Swinehart; Katherine M. Bland; Z. Logan Holley; Andrew J. Lopuch; Zachary O. Casey; Christopher J. Handwerk; George S. Vidal
Dysfunctional dendritic arborization is a key feature of many developmental neurological disorders. Across various human brain regions, basal dendritic complexity is known to increase along a caudal-to-rostral gradient. We recently discovered that basal dendritic complexity of layer II/III cortical pyramidal neurons in the mouse increases along a caudomedial-to-rostrolateral gradient spanning multiple
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LRP4 LDLα repeats of astrocyte enhance dendrite arborization of the neuron Mol. Brain (IF 4.686) Pub Date : 2020-12-10 Min Yan; Amin Guo; Peng Chen; Hongyang Jing; Dongyan Ren; Yanzi Zhong; Yongqiang Wu; Erkang Fei; Xinsheng Lai; Suqi Zou; Shunqi Wang
The low-density lipoprotein receptor-related protein 4 (LRP4) is essential for inducing the neuromuscular junction (NMJ) formation in muscle fibers, and LRP4 plays a critical role in dendritic development and synaptogenesis in the central nervous system (CNS). As a single transmembrane protein, LRP4 contains an enormously sizeable extracellular domain (ECD), containing multiple LDLα repeats in the
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Translational changes induced by acute sleep deprivation uncovered by TRAP-Seq Mol. Brain (IF 4.686) Pub Date : 2020-12-03 Lisa C. Lyons; Snehajyoti Chatterjee; Yann Vanrobaeys; Marie E. Gaine; Ted Abel
Sleep deprivation is a global health problem adversely affecting health as well as causing decrements in learning and performance. Sleep deprivation induces significant changes in gene transcription in many brain regions, with the hippocampus particularly susceptible to acute sleep deprivation. However, less is known about the impacts of sleep deprivation on post-transcriptional gene regulation. To
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Manganese-enhanced MRI depicts a reduction in brain responses to nociception upon mTOR inhibition in chronic pain rats Mol. Brain (IF 4.686) Pub Date : 2020-11-23 Myeounghoon Cha; Songyeon Choi; Kyeongmin Kim; Bae Hwan Lee
Neuropathic pain induced by a nerve injury can lead to chronic pain. Recent studies have reported hyperactive neural activities in the nociceptive-related area of the brain as a result of chronic pain. Although cerebral activities associated with hyperalgesia and allodynia in chronic pain models are difficult to represent with functional imaging techniques, advances in manganese (Mn)-enhanced magnetic
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Altered striatal dopamine levels in Parkinson’s disease VPS35 D620N mutant transgenic aged mice Mol. Brain (IF 4.686) Pub Date : 2020-12-01 Sarivin Vanan; Xiaoxia Zeng; Sook Yoong Chia; Katarina Varnäs; Mei Jiang; Ke Zhang; Wuan Ting Saw; Parasuraman Padmanabhan; Wei-Ping Yu; Zhi-Dong Zhou; Christer Halldin; Balázs Gulyás; Eng-King Tan; Li Zeng
Vacuolar protein sorting 35 (VPS35) is a major component of the retromer complex that mediates the retrograde transport of cargo proteins from endosomes to the trans-Golgi network. Mutations such as D620N in the VPS35 gene have been identified in patients with autosomal dominant Parkinson’s disease (PD). However, it remains poorly understood whether and how VPS35 deficiency or mutation contributes
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Zonisamide can ameliorate the voltage-dependence alteration of the T-type calcium channel CaV3.1 caused by a mutation responsible for spinocerebellar ataxia Mol. Brain (IF 4.686) Pub Date : 2020-11-26 Naoyuki Hara; Hiroyuki Morino; Yukiko Matsuda; Kenichi Satoh; Kouichi Hashimoto; Hirofumi Maruyama; Hideshi Kawakami
Spinocerebellar ataxia (SCA) 42 is caused by a mutation in CACNA1G, which encodes the low voltage-gated calcium channel CaV3.1 (T-type). Patients with SCA42 exhibit a pure form of cerebellar ataxia. We encountered a patient with the p.Arg1715His mutation, suffering from intractable resting tremor, particularly head tremor. This symptom improved with the administration of low-dose of zonisamide (ZNS)
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Nicotinamide, a vitamin B3 ameliorates depressive behaviors independent of SIRT1 activity in mice Mol. Brain (IF 4.686) Pub Date : 2020-11-23 Zhuxi Liu; Caiqin Li; Xuelian Fan; Yifang Kuang; Xu Zhang; Lei Chen; Jinjing Song; Ying Zhou; Eiki Takahashi; Guang He; Weidong Li
Sirtuin 1 (SIRT1), is a nicotinamide adenine dinucleotide (NAD+)-dependent protein deacetylase and a candidate gene for depression. Nicotinamide (NAM), a form of vitamin B3, is reported as a potential inhibitor of SIRT1. Our previous study found that the 24-h-restraint stress could induce long-term depressive-like phenotypes in mice. These mice displayed increased SIRT1 activity. Here, we studied whether
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CCL2 facilitates spinal synaptic transmission and pain via interaction with presynaptic CCR2 in spinal nociceptor terminals Mol. Brain (IF 4.686) Pub Date : 2020-11-23 Sui-Bin Ma; Hang Xian; Wen-Bin Wu; Shuo-Yao Ma; Yu-Ke Liu; Yu-Tong Liang; Huan Guo; Jun-Jun Kang; Ying-Ying Liu; Hui Zhang; Sheng-Xi Wu; Ceng Luo; Rou-Gang Xie
Previous studies have shown that CCL2 may cause chronic pain, but the exact mechanism of central sensitization is unclear. In this article, we further explore the presynaptic role of CCL2. Behavioral experiments show that intervertebral foramen injection CCR2 antagonists into dorsal root ganglion (DRG) can inhibit the inflammatory pain caused by CCL2 in spinal cord. We raised the question of the role
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Chd8 mutation in oligodendrocytes alters microstructure and functional connectivity in the mouse brain Mol. Brain (IF 4.686) Pub Date : 2020-11-23 Atsuki Kawamura; Yoshifumi Abe; Fumiko Seki; Yuta Katayama; Masaaki Nishiyama; Norio Takata; Kenji F. Tanaka; Hideyuki Okano; Keiichi I. Nakayama
CHD8 encodes a chromatin-remodeling factor and is one of the most recurrently mutated genes in individuals with autism spectrum disorder (ASD). Although we have recently shown that mice heterozygous for Chd8 mutation manifest myelination defects and ASD-like behaviors, the detailed mechanisms underlying ASD pathogenesis have remained unclear. Here we performed diffusion tensor imaging (DTI) and resting-state
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Focal loss of the paranodal domain protein Neurofascin155 in the internal capsule impairs cortically induced muscle activity in vivo Mol. Brain (IF 4.686) Pub Date : 2020-11-23 Kazuo Kunisawa; Nobuhiko Hatanaka; Takeshi Shimizu; Kenta Kobayashi; Yasuyuki Osanai; Akihiro Mouri; Qian Shi; Manzoor A. Bhat; Atsushi Nambu; Kazuhiro Ikenaka
Paranodal axoglial junctions are essential for rapid nerve conduction and the organization of axonal domains in myelinated axons. Neurofascin155 (Nfasc155) is a glial cell adhesion molecule that is also required for the assembly of these domains. Previous studies have demonstrated that general ablation of Nfasc155 disorganizes these domains, reduces conduction velocity, and disrupts motor behaviors
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Enhanced bodily states of fear facilitates bias perception of fearful faces Mol. Brain (IF 4.686) Pub Date : 2020-11-23 Won-Mo Jung; Ye-Seul Lee; In-Seon Lee; Christian Wallraven; Yeonhee Ryu; Younbyoung Chae
We investigated whether enhanced interoceptive bodily states of fear would facilitate recognition of the fearful faces. Participants performed an emotional judgment task after a bodily imagery task inside a functional magnetic resonance imaging scanner. In the bodily imagery task, participants were instructed to imagine feeling the bodily sensations of two specific somatotopic patterns: a fear-associated
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MeCP2 gates spatial learning-induced alternative splicing events in the mouse hippocampus Mol. Brain (IF 4.686) Pub Date : 2020-11-17 David V. C. Brito; Kubra Gulmez Karaca; Janina Kupke; Lukas Frank; Ana M. M. Oliveira
Long-term memory formation is supported by functional and structural changes of neuronal networks, which rely on de novo gene transcription and protein synthesis. The modulation of the neuronal transcriptome in response to learning depends on transcriptional and post-transcriptional mechanisms. DNA methylation writers and readers regulate the activity-dependent genomic program required for memory consolidation
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WNT signaling suppresses oligodendrogenesis via Ngn2-dependent direct inhibition of Olig2 expression Mol. Brain (IF 4.686) Pub Date : 2020-11-13 Min Jiang; Dan Yu; Binghua Xie; Hao Huang; Wenwen Lu; Mengsheng Qiu; Zhong-Min Dai
Olig2 transcription factor is essential for the maintenance of neural progenitor cells (NPCs) in the pMN domain and their sequential specification into motor neurons (MNs) and oligodendrocyte precursor cells (OPCs). The expression of Olig2 rapidly declines in newly generated MNs. However, Olig2 expression persists in later-born OPCs and antagonizes the expression of MN-related genes. The mechanism
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Frequency and methylation status of selected retrotransposition competent L1 loci in amyotrophic lateral sclerosis Mol. Brain (IF 4.686) Pub Date : 2020-11-13 Abigail L. Savage; Ana Illera Lopez; Alfredo Iacoangeli; Vivien J. Bubb; Bradley Smith; Claire Troakes; Nada Alahmady; Sulev Koks; Gerald G. Schumann; Ammar Al-Chalabi; John P. Quinn
Long interspersed element-1 (LINE-1/L1) is the only autonomous transposable element in the human genome that currently mobilises in both germline and somatic tissues. Recent studies have identified correlations between altered retrotransposon expression and the fatal neurodegenerative disease amyotrophic lateral sclerosis (ALS) in a subset of patients. The risk of an individual developing ALS is dependent
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Neuregulin-1 inhibits CoCl2-induced upregulation of excitatory amino acid carrier 1 expression and oxidative stress in SH-SY5Y cells and the hippocampus of mice Mol. Brain (IF 4.686) Pub Date : 2020-11-13 Han-Byeol Kim; Ji-Young Yoo; Seung-Yeon Yoo; Jun-Ho Lee; Wonseok Chang; Hye-Sun Kim; Tai-Kyoung Baik; Ran-Sook Woo
Excitatory amino acid carrier 1 (EAAC1) is an important subtype of excitatory amino acid transporters (EAATs) and is the route for neuronal cysteine uptake. CoCl2 is not only a hypoxia-mimetic reagent but also an oxidative stress inducer. Here, we found that CoCl2 induced significant EAAC1 overexpression in SH-SY5Y cells and the hippocampus of mice. Transient transfection of EAAC1 reduced CoCl2-induced
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Correction to: Ascending noradrenergic excitation from the locus coeruleus to the anterior cingulate cortex Mol. Brain (IF 4.686) Pub Date : 2020-11-13 Kohei Koga; Akihiro Yamada; Qian Song; Xu-Hui Li; Qi-Yu Chen; Ren-Hao Liu; Jun Ge; Cheng Zhan; Hidemasa Furue; Min Zhuo; Tao Chen
An amendment to this paper has been published and can be accessed via the original article.
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Touchscreen-based location discrimination and paired associate learning tasks detect cognitive impairment at an early stage in an App knock-in mouse model of Alzheimer’s disease Mol. Brain (IF 4.686) Pub Date : 2020-11-13 Md. Ali Bin Saifullah; Okiru Komine; Yutao Dong; Kazuya Fukumoto; Akira Sobue; Fumito Endo; Takashi Saito; Takaomi C. Saido; Koji Yamanaka; Hiroyuki Mizoguchi
Alzheimer's disease (AD) is a progressive neurodegenerative disorder characterized by cognitive decline with accumulation of amyloid beta (Aβ) and neurofibrillary tangles that usually begins 15–30 years before clinical diagnosis. Rodent models that recapitulate aggressive Aβ and/or the pathology of neurofibrillary tangles are essential for AD research. Accordingly, non-invasive early detection systems
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Leptin down-regulates KCC2 activity and controls chloride homeostasis in the neonatal rat hippocampus Mol. Brain (IF 4.686) Pub Date : 2020-11-12 Camille Dumon; Yasmine Belaidouni; Diabe Diabira; Suzanne M. Appleyard; Gary A. Wayman; Jean-Luc Gaiarsa
The canonical physiological role of leptin is to regulate hunger and satiety acting on specific hypothalamic nuclei. Beyond this key metabolic function; leptin also regulates many aspects of development and functioning of neuronal hippocampal networks throughout life. Here we show that leptin controls chloride homeostasis in the developing rat hippocampus in vitro. The effect of leptin relies on the
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The Sigma 2 receptor promotes and the Sigma 1 receptor inhibits mu-opioid receptor-mediated antinociception Mol. Brain (IF 4.686) Pub Date : 2020-11-11 Pilar Sánchez-Blázquez; Elsa Cortés-Montero; María Rodríguez-Muñoz; Manuel Merlos; Javier Garzón-Niño
The Sigma-1 receptor (σ1R) has emerged as an interesting pharmacological target because it inhibits analgesia mediated by mu-opioid receptors (MOR), and also facilitates the development of neuropathic pain. Based on these findings, the recent cloning of the Sigma-2 receptor (σ2R) led us to investigate its potential role as a regulator of opioid analgesia and of pain hypersensitivity in σ2R knockout
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Functional identification of potential non-canonical N-glycosylation sites within Cav3.2 T-type calcium channels Mol. Brain (IF 4.686) Pub Date : 2020-11-11 Vendula Ficelova; Ivana A. Souza; Leos Cmarko; Maria A. Gandini; Robin N. Stringer; Gerald W. Zamponi; Norbert Weiss
Low-voltage-activated T-type calcium channels are important contributors to nervous system function. Post-translational modification of these channels has emerged as an important mechanism to control channel activity. Previous studies have documented the importance of asparagine (N)-linked glycosylation and identified several asparagine residues within the canonical consensus sequence N-X-S/T that
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Neuronal activity regulates alternative exon usage Mol. Brain (IF 4.686) Pub Date : 2020-11-10 Johanna Denkena; Andrea Zaisser; Barbara Merz; Bertram Klinger; Dietmar Kuhl; Nils Blüthgen; Guido Hermey
Neuronal activity-regulated gene transcription underlies plasticity-dependent changes in the molecular composition and structure of neurons. A large number of genes regulated by different neuronal plasticity inducing pathways have been identified, but altered gene expression levels represent only part of the complexity of the activity-regulated transcriptional program. Alternative splicing, the differential
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Protrudin-deficient mice manifest depression-like behavior with abnormalities in activity, attention, and cued fear-conditioning Mol. Brain (IF 4.686) Pub Date : 2020-11-10 Michiko Shirane; Hirotaka Shoji; Yutaka Hashimoto; Hiroyuki Katagiri; Shizuka Kobayashi; Toshiya Manabe; Tsuyoshi Miyakawa; Keiichi I. Nakayama
Protrudin is a protein that resides in the membrane of the endoplasmic reticulum and is highly expressed in the nervous system. Although mutations in the human protrudin gene (ZFYVE27, also known as SPG33) give rise to hereditary spastic paraplegia (HSP), the physiological role of the encoded protein has been largely unclear. We therefore generated mice deficient in protrudin and subjected them to
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Selective role of the translin/trax RNase complex in hippocampal synaptic plasticity Mol. Brain (IF 4.686) Pub Date : 2020-11-10 Alan Jung Park; Mahesh Shivarama Shetty; Jay M. Baraban; Ted Abel
Activity-dependent local protein synthesis is critical for synapse-specific, persistent plasticity. Abnormalities in local protein synthesis have been implicated in psychiatric disorders. We have recently identified the translin/trax microRNA-degrading enzyme as a novel mediator of protein synthesis at activated synapses. Additionally, translin knockout (KO) mice, which lack translin/trax, exhibit
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Intrinsic braking role of descending locus coeruleus noradrenergic neurons in acute and chronic itch in mice Mol. Brain (IF 4.686) Pub Date : 2020-10-27 Keisuke Koga; Yuto Shiraishi; Ryo Yamagata; Hidetoshi Tozaki-Saitoh; Miho Shiratori-Hayashi; Makoto Tsuda
Itch is defined as an unpleasant sensation that provokes a desire to scratch. Our understanding of neuronal circuits for itch information transmission and processing in the spinal dorsal horn (SDH) has progressively advanced following the identification of SDH neuron subsets that are crucial for scratching behavior in models of itch. However, little is known about the control of acute and chronic itch
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The voltage-gated proton channel Hv1 contributes to neuronal injury and motor deficits in a mouse model of spinal cord injury Mol. Brain (IF 4.686) Pub Date : 2020-10-20 Madhuvika Murugan; Jiaying Zheng; Gongxiong Wu; Rochelle Mogilevsky; Xin Zheng; Peiwen Hu; Junfang Wu; Long-Jun Wu
Traumatic injury to the spinal cord initiates a series of pathological cellular processes that exacerbate tissue damage at and beyond the original site of injury. This secondary damage includes oxidative stress and inflammatory cascades that can lead to further neuronal loss and motor deficits. Microglial activation is an essential component of these secondary signaling cascades. The voltage-gated
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Brain transcriptome analysis reveals subtle effects on mitochondrial function and iron homeostasis of mutations in the SORL1 gene implicated in early onset familial Alzheimer’s disease Mol. Brain (IF 4.686) Pub Date : 2020-10-19 Karissa Barthelson; Stephen Martin Pederson; Morgan Newman; Michael Lardelli
To prevent or delay the onset of Alzheimer’s disease (AD), we must understand its molecular basis. The great majority of AD cases arise sporadically with a late onset after 65 years of age (LOAD). However, rare familial cases of AD can occur due to dominant mutations in a small number of genes that cause an early onset prior to 65 years of age (EOfAD). As EOfAD and LOAD share similar pathologies and
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Stimulation-induced differential redistributions of clathrin and clathrin-coated vesicles in axons compared to soma/dendrites Mol. Brain (IF 4.686) Pub Date : 2020-10-16 Jung-Hwa Tao-Cheng
Clathrin-mediated endocytosis plays an important role in the recycling of synaptic vesicle in presynaptic terminals, and in the recycling of transmitter receptors in neuronal soma/dendrites. The present study uses electron microscopy (EM) and immunogold EM to document the different categories of clathrin-coated vesicles (CCV) and pits (CCP) in axons compared to soma/dendrites, and the depolarization-induced
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α2-Antiplasmin as a potential regulator of the spatial memory process and age-related cognitive decline Mol. Brain (IF 4.686) Pub Date : 2020-10-15 Eri Kawashita; Keiichi Ishihara; Haruko Miyaji; Yu Tanishima; Akiko Kiriyama; Osamu Matsuo; Satoshi Akiba
α2-Antiplasmin (α2AP), a principal physiological plasmin inhibitor, is mainly produced by the liver and kidneys, but it is also expressed in several parts of the brain, including the hippocampus and cerebral cortex. Our previous study demonstrated that α2AP knockout mice exhibit spatial memory impairment in comparison to wild-type mice, suggesting that α2AP is necessary for the fetal and/or neonatal
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Inhibitory synaptic transmissions to the bed nucleus of the stria terminalis neurons projecting to the ventral tegmental area are enhanced in rats exposed to chronic mild stress Mol. Brain (IF 4.686) Pub Date : 2020-10-15 Ryuto Hara; Daiki Takahashi; Tatsuhiro Takehara; Taiju Amano; Masabumi Minami
The comorbidities of depression and chronic pain have long been recognized in the clinic, and several preclinical studies have demonstrated depression-like behaviors in animal models of chronic pain. These findings suggest a common neuronal basis for depression and chronic pain. Recently, we reported that the mesolimbic dopaminergic system was tonically suppressed during chronic pain by enhanced inhibitory
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AAV9-Retro mediates efficient transduction with axon terminal absorption and blood–brain barrier transportation Mol. Brain (IF 4.686) Pub Date : 2020-10-14 Kunzhang Lin; Xin Zhong; Lei Li; Min Ying; Tian Yang; Zhijian Zhang; Xiaobin He; Fuqiang Xu
Recombinant adeno-associated viruses (rAAVs), particularly those that permit efficient gene transfer to neurons from axonal terminals or across the blood–brain barrier, are useful vehicles for structural and functional studies of the neural circuit and for the treatment of many gene-deficient brain diseases that need to compensate for the correct genes in every cell in the whole brain. However, AAVs
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Endosomal dysfunction in iPSC-derived neural cells from Parkinson’s disease patients with VPS35 D620N Mol. Brain (IF 4.686) Pub Date : 2020-10-08 Keiko Bono; Chikako Hara-Miyauchi; Shunsuke Sumi; Hisayoshi Oka; Yasuyuki Iguchi; Hirotaka James Okano
Mutations in the Vacuolar protein sorting 35 (VPS35) gene have been linked to familial Parkinson’s disease (PD), PARK17. VPS35 is a key component of the retromer complex, which plays a central role in endosomal trafficking. However, whether and how VPS35 deficiency or mutation contributes to PD pathogenesis remain unclear. Here, we analyzed human induced pluripotent stem cell (iPSC)-derived neurons
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Decreased intrinsic excitability of cerebellar Purkinje cells following optokinetic learning in mice Mol. Brain (IF 4.686) Pub Date : 2020-10-07 Yong Gyu Kim; Sang Jeong Kim
The optokinetic response (OKR), a reflexive eye movement evoked by a motion of the visual field, is known to adapt its strength to cope with an environmental change throughout life, which is a type of cerebellum-dependent learning. Previous studies suggested that OKR learning induces changes in in-vivo spiking activity and synaptic transmission of the cerebellar Purkinje cell (PC). Despite the recent
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Overexpression of Slit2 decreases neuronal excitotoxicity, accelerates glymphatic clearance, and improves cognition in a multiple microinfarcts model Mol. Brain (IF 4.686) Pub Date : 2020-10-07 Xiao-fei He; Ge Li; Li-li Li; Ming-yue Li; Feng-yin Liang; Xi Chen; Xi-quan Hu
Cerebral microinfarcts (MIs) lead to progressive cognitive impairments in the elderly, and there is currently no effective preventative strategy due to uncertainty about the underlying pathogenic mechanisms. One possibility is the dysfunction of GABAergic transmission and ensuing excitotoxicity. Dysfunction of GABAergic transmission induces excitotoxicity, which contributes to stroke pathology, but
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Fear response-based prediction for stress susceptibility to PTSD-like phenotypes Mol. Brain (IF 4.686) Pub Date : 2020-10-07 Min-Jae Jeong; Changhee Lee; Kibong Sung; Jung Hoon Jung; Jung Hyun Pyo; Joung-Hun Kim
Most individuals undergo traumatic stresses at some points in their life, but only a small proportion develop stress-related disorders such as anxiety diseases and posttraumatic stress disorder (PTSD). Although stress susceptibility is one determinant of mental disorders, the underlying mechanisms and functional implication remain unclear yet. We found that an increased amount of freezing that animals
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Peptidome analysis of cerebrospinal fluid in neonates with hypoxic-ischemic brain damage Mol. Brain (IF 4.686) Pub Date : 2020-10-02 Xuewen Hou; Zijun Yuan; Xuan Wang; Rui Cheng; Xiaoguang Zhou; Jie Qiu
Hypoxic-ischemic brain injury (HIBD) causes neonatal death and serious neurological disability; however, there are currently no promising therapies for it excepting cooling. Therefore, in this study, we used peptidome analysis to identify differentially expressed peptides in cerebrospinal fluid (CSF) of neonates with HIBD or controls, which may give a foundation for finding new promising drugs of neonatal
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GPR68 deletion impairs hippocampal long-term potentiation and passive avoidance behavior Mol. Brain (IF 4.686) Pub Date : 2020-09-29 Yuanyuan Xu; Mike T. Lin; Xiang-ming Zha
Increased neural activities reduced pH at the synaptic cleft and interstitial spaces. Recent studies have shown that protons function as a neurotransmitter. However, it remains unclear whether protons signal through a metabotropic receptor to regulate synaptic function. Here, we showed that GPR68, a proton-sensitive GPCR, exhibited wide expression in the hippocampus, with higher expression observed
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The VEGF inhibitor vatalanib regulates AD pathology in 5xFAD mice Mol. Brain (IF 4.686) Pub Date : 2020-09-25 Seong Gak Jeon; Hyun-ju Lee; HyunHee Park; Kyung-Min Han; Hyang-Sook Hoe
Alzheimer’s disease (AD) is a highly prevalent neurodegenerative disease characterized by Aβ accumulation and tau hyperphosphorylation. Epidemiological evidence for a negative correlation between cancer and AD has led to the proposed use of tyrosine kinase inhibitors (TKIs) such as dasatinib and masitinib for AD, with reported beneficial effects in the AD brain. The TKI vatalanib inhibits angiogenesis
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LncRNA MALAT1 facilitates inflammasome activation via epigenetic suppression of Nrf2 in Parkinson’s disease Mol. Brain (IF 4.686) Pub Date : 2020-09-24 Li-Jun Cai; Li Tu; Xiao-Mo Huang; Jia Huang; Nan Qiu; Guang-Hong Xie; Jian-Xiong Liao; Wei Du; Ying-Yue Zhang; Jin-Yong Tian
The goal of the present study was to elucidate the mechanism by which long non-coding RNA metastasis-associated lung adenocarcinoma transcript 1 (lncRNA MALAT1) promotes inflammation in Parkinson’s disease (PD). 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was used to induce PD development in C57BL/6 mice, and tyrosine hydroxylase (TH) expression was analysed by immunohistochemical analysis
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Ketamine normalizes high-gamma power in the anterior cingulate cortex in a rat chronic pain model. Mol. Brain (IF 4.686) Pub Date : 2020-09-23 Isabel D Friesner,Erik Martinez,Haocheng Zhou,Jonathan Douglas Gould,Anna Li,Zhe Sage Chen,Qiaosheng Zhang,Jing Wang
Chronic pain alters cortical and subcortical plasticity, causing enhanced sensory and affective responses to peripheral nociceptive inputs. Previous studies have shown that ketamine had the potential to inhibit abnormally amplified affective responses of single neurons by suppressing hyperactivity in the anterior cingulate cortex (ACC). However, the mechanism of this enduring effect has yet to be understood
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Kappa opioid receptors in the central amygdala modulate spinal nociceptive processing through an action on amygdala CRF neurons. Mol. Brain (IF 4.686) Pub Date : 2020-09-18 Guangchen Ji,Volker Neugebauer
The amygdala plays an important role in the emotional-affective aspects of behaviors and pain, but can also modulate sensory aspect of pain (“nociception”), likely through coupling to descending modulatory systems. Here we explored the functional coupling of the amygdala to spinal nociception. We found that pharmacological activation of neurons in the central nucleus of the amygdala (CeA) increased