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Noémie Remacle, Patrick Forny, Hong-Phuc Cudré-Cung, Mary Gonzalez-Melo, Sónia do Vale-Pereira, Hugues Henry, Tony Teav, Hector Gallart-Ayala, Olivier Braissant, Matthias Baumgartner, Diana Ballhausen
BACKGROUND: Methylmalonic aciduria (MMAuria) is an inborn error of metabolism leading to neurological deterioration. In this study, we used 3D organotypic brain cell cultures derived from embryos of a brain-specific Mut-/- (brain KO) mouse to investigate mechanisms leading to brain damage. We challenged our in vitro model by a catabolic stress (temperature shift). RESULTS: Typical metabolites for MMAuria as well as a massive NH4+ increase were found in the media of brain KO cultures...
June 18, 2018: Molecular Genetics and Metabolism
Roumei Xing, Fang Liu, Yiqing Yang, Xueqin Cui, Tongtong Wang, Ling Xie, Yongliang Zhao, Lei Fang, Tingfang Yi, Biao Zheng, Mingyao Liu, Huaqing Chen
GPR54 is highly expressed in the central nervous system and plays a crucial role in pubertal development. However, GRP54 is also expressed in the immune system, implying possible immunoregulatory functions. Here we investigated the role of GPR54 in T cell and immune tolerance. GPR54 deficiency led to an enlarged thymus, an increased number of thymocytes, and altered thymic micro-architecture starting around puberty, indicating GPR54 function in T-cell development through its regulatory effect on the gonadal system...
June 2018: Science China. Life Sciences
Wenguang Chang, Junfang Teng
Demyelinating diseases, such as multiple sclerosis, are known to result from acute or chronic injury to the myelin sheath and inadequate remyelination. Its underlying molecular mechanisms, however, remain unclear. The transcription factor prospero homeobox 1 (Prox1) plays an essential role during embryonic development of the central nervous system and cell differentiation. Thus, we aimed to investigate the role of Prox1 in the survival and differentiation of oligodendrocytes. Cell viability was measured by MTT assay...
June 20, 2018: Acta Biochimica et Biophysica Sinica
V M Vostrikov, N A Uranova
AIM: Oligodendrocyte abnormalities are thought to be one of the key cellular pathologies involved in disturbances of neuronal connectivity in schizophrenia. MATERIAL AND METHODS: The density of oligodendrocytes in layer III of the prefrontal cortex, BA10, in schizophrenia (n=20) was compared to controls (n=20) using optical dissector method. MANCOVA was applied for group comparisons. RESULTS AND CONCLUSION: The density of oligodendrocytes was significantly lower in each sublayers of layer III (≤20% p≤0...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
O V Vikhreva, V I Rakhmanova, D D Orlovskaya, N A Uranova
AIM: Previously the authors have reported the ultrastructural pathology and deficits of oligodendrocytes in gray and white matter of the prefrontal cortex in continuous paranoid schizophrenia. The aim of the present work was to study the effects of microglia on the ultrastructure of oligodendrocytes in white matter underlying the prefrontal cortex (BA10) in attack-like schizophrenia. MATERIAL AND METHODS: Postmortem morphometric electron microscopic study of oligodendrocytes in close apposition to microglia was performed in white matter underlying the prefrontal cortex (BA10)...
2018: Zhurnal Nevrologii i Psikhiatrii Imeni S.S. Korsakova
Yana Zorina, Jason Stricker, Anthony O Caggiano, Donald C Button
In multiple sclerosis (MS), demyelinated CNS lesions fail to sufficiently remyelinate, despite the presence of oligodendrocyte precursor cells (OPCs) capable of differentiating into mature oligodendrocytes. MS lesions contain damaged myelin debris that can inhibit OPC maturation and hinder repair. rHIgM22 is an experimental human recombinant IgM antibody that promotes remyelination in animal models and is being examined in patients with MS. rHIgM22 binds to CNS myelin and partially rescues OPC process outgrowth on myelin...
June 20, 2018: Scientific Reports
Karen Lariosa-Willingham, Dmitri Leonoudakis
Multiple sclerosis (MS) is an autoimmune disease that involves an immune-mediated inflammatory response in the central nervous system and optic nerve resulting in demyelination and neural degeneration, the cause of which is unknown. The adult central nervous system has the capacity to remyelinate axons by generating new oligodendrocytes (OLs). To identify clinical candidate compounds that may promote remyelination, we have developed a high-throughput screening (HTS) assay to identify compounds that promote the differentiation of oligodendrocyte precursor cells (OPCs) into OLs...
June 2018: Current Protocols in Cell Biology
Mark R Griffiths, Marina Botto, B Paul Morgan, J W Neal, P Gasque
Microglia and non-professional immune cells (endothelial cells, neurons) participate in the recognition and removal of pathogens and tissue-debris in the injured CNS through major pro-inflammatory processes. However, the mechanisms involved in regulating these responses remain ill-characterised. We herein show that CD93 also known as complement C1qRp/AA4 stem cell marker has an important role in the regulation of inflammatory processes. The role of CD93 was evaluated in two models of neuroinflammation. We used the MOG-experimental autoimmune encephalomyelitis (EAE) model and the antibody-dependent EAE (ADEAE) which were induced in wild type and CD93 knockout mice...
June 20, 2018: Immunology
Julie C Savage, Katherine Picard, Fernando González-Ibáñez, Marie-Ève Tremblay
The first electron microscope was constructed in 1931. Several decades later, techniques were developed to allow the first ultrastructural analysis of microglia by transmission electron microscopy (EM). In the 50 years that followed, important roles of microglia have been identified, specifically due to the ultrastructural resolution currently available only with EM. In particular, the addition of electron-dense staining using immunohistochemical EM methods has allowed the identification of microglial cell bodies, as well as processes, which are difficult to recognize in EM, and to uncover their complex interactions with neurons and synapses...
2018: Frontiers in Immunology
Qiang Li, Hengli Zhao, Pengyu Pan, Xufang Ru, Shilun Zuo, Jie Qu, Bin Liao, Yujie Chen, Huaizhen Ruan, Hua Feng
Progressive white matter (WM) impairments caused by subarachnoid hemorrhage (SAH) contribute to cognitive deficits and poor clinical prognoses; however, their pathogenetic mechanisms are poorly understood. We investigated the role of nexilin and oligodendrocyte progenitor cell (OPC)-mediated repair in a mouse model of experimental SAH generated via left endovascular perforation. Nexilin expression was enhanced by the elevated migration of OPCs after SAH. Knocking down nexilin by siRNA reduced OPC migration both in vitro and in vivo and abridged WM repair...
2018: Frontiers in Neurology
Yuan Gao, Ming-Yang Zhang, Tao Wang, Yan-Yan Fan, Lin-Sheng Yu, Guang-Hua Ye, Zu-Feng Wang, Cheng Gao, Hao-Chen Wang, Cheng-Liang Luo, Lu-Yang Tao
Interleukin-33 (IL-33) is a member of the interleukin-1 (IL-1) cytokine family and an extracellular ligand for the orphan IL-1 receptor ST2. Accumulated evidence shows that the IL-33/ST2 axis plays a crucial role in the pathogenesis of central nervous system (CNS) diseases and injury, including traumatic brain injury (TBI). However, the roles and molecular mechanisms of the IL-33/ST2 axis after TBI remain poorly understood. In this study, we investigated the role of IL-33/ST2 signaling in mouse TBI-induced brain edema and neurobehavioral deficits, and further exploited underlying mechanisms, using salubrinal (SAL), the endoplasmic reticulum (ER) stress inhibitor and anti-ST2L...
2018: Frontiers in Cellular Neuroscience
Chan-Il Choi, Hyesook Yoon, Kristen L Drucker, Monica R Langley, Laurel Kleppe, Isobel A Scarisbrick
Thrombin is frequently increased in the CNS after injury yet little is known regarding its effects on neural stem cells. Here we show that the subventricular zone (SVZ) of adult mice lacking the high affinity receptor for thrombin, proteinase activated receptor 1 (PAR1), show increased numbers of Sox2+ and Ki-67+ self-renewing neural stem cells (NSCs) and Olig2+ oligodendrocyte progenitors. SVZ NSCs derived from PAR1-knockout mice, or treated with a PAR1 small molecule inhibitor (SCH79797), exhibited enhanced capacity for self-renewal in vitro, including increases in neurosphere formation and BrdU incorporation...
June 19, 2018: Scientific Reports
Chuntao Zhao, Chen Dong, Magali Frah, Yaqi Deng, Corentine Marie, Feng Zhang, Lingli Xu, Zhixing Ma, Xinran Dong, Yifeng Lin, Scott Koenig, Brahim Nait-Oumesmar, Donna M Martin, Laiman N Wu, Mei Xin, Wenhao Zhou, Carlos Parras, Q Richard Lu
Disruptive mutations in chromatin remodeler CHD8 cause autism spectrum disorders, exhibiting widespread white matter abnormalities; however, the underlying mechanisms remain elusive. We show that cell-type specific Chd8 deletion in oligodendrocyte progenitors, but not in neurons, results in myelination defects, revealing a cell-intrinsic dependence on CHD8 for oligodendrocyte lineage development, myelination and post-injury remyelination. CHD8 activates expression of BRG1-associated SWI/SNF complexes that in turn activate CHD7, thus initiating a successive chromatin remodeling cascade that orchestrates oligodendrocyte lineage progression...
June 18, 2018: Developmental Cell
Marcus K Giacci, Carole A Bartlett, Nicole M Smith, K Swaminathan Iyer, Lillian M Toomey, Haibo Jiang, Paul Guagliardo, Matt R Kilburn, Melinda Fitzgerald
Loss of function following injury to the central nervous system is worsened by secondary degeneration of neurons and glia surrounding the injury and initiated by oxidative damage. However, it is not yet known which cellular populations and structures are most vulnerable to oxidative damage in vivo Using Nanoscale secondary ion mass spectrometry (NanoSIMS), oxidative damage was semi-quantified within cellular subpopulations and structures of optic nerve vulnerable to secondary degeneration, following a partial transection of the optic nerve in adult female PVG rats...
June 18, 2018: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
Denise M Piscopo, Aldis P Weible, Mary K Rothbart, Michael I Posner, Cristopher M Niell
Recent reports have begun to elucidate mechanisms by which learning and experience produce white matter changes in the brain. We previously reported changes in white matter surrounding the anterior cingulate cortex in humans after 2-4 weeks of meditation training. We further found that low-frequency optogenetic stimulation of the anterior cingulate in mice increased time spent in the light in a light/dark box paradigm, suggesting decreased anxiety similar to what is observed following meditation training. Here, we investigated the impact of this stimulation at the cellular level...
June 18, 2018: Proceedings of the National Academy of Sciences of the United States of America
Mohammad Abu-Rub, Robert H Miller
Myelination is critical for the normal functioning of the central nervous system (CNS) in vertebrates. Conditions in which the development of myelin is perturbed result in severely compromised individuals often with shorter lifespans, while loss of myelin in the adult results in a variety of functional deficits. Although some form of spontaneous remyelination often takes place, the repair process as a whole often fails. Several lines of evidence suggest it is feasible to develop strategies that enhance the capacity of the CNS to undergo remyelination and potentially reverse functional deficits...
June 15, 2018: Brain Sciences
Wenhui Huang, Xianshu Bai, Laura Stopper, Bogdan Catalin, Luciana Politti Cartarozzi, Anja Scheller, Frank Kirchhoff
NG2 glia are self-renewal cells widely populating the entire central nervous system (CNS). The differentiation potential of NG2 glia in the brain has been systematically studied. However, the fate of NG2 glia in the spinal cord during development and after injury is still unclear. Here, we took advantage of faithful expression of Cre in NG2-CreERT2 knock-in mice to demonstrate that spinal NG2 glia remain committed to the oligodendrocyte (OL) lineage and generate OLs, but not astrocytes or neurons, during development...
June 15, 2018: Neuroscience
Martin S Weber, Tobias Derfuss, Wolfgang Brück
No abstract text is available yet for this article.
June 18, 2018: JAMA Neurology
Michele Ori, Valeria Gambacorta, Giampietro Ricci, Mario Faralli
The term vestibular paroxysmia (VP) was introduced for the first time by Brandt and Dieterich in 1994. In 2016, the Barany Society formulated the International Classification of VP, focusing in particular on the number and duration of attacks, on the differential diagnosis and on the therapy. Ephaptic discharges in the proximal part of the eighth cranial nerve, which is covered by oligodendrocytes, are assumed to be the neural basis of VP. We report the first case in literature of an onset of symptoms and signs typical of VP in a young man following acute unilateral vestibular loss not combined with auditory symptoms...
March 6, 2018: Audiology Research
Kenji Imai, Tomomi Kotani, Hiroyuki Tsuda, Tomoko Nakano, Takafumi Ushida, Akira Iwase, Taku Nagai, Shinya Toyokuni, Akio Suzumura, Fumitaka Kikkawa
The aim of the present study was to investigate long-term outcomes of the offspring in a lipopolysaccharide (LPS)-induced maternal immune activation (MIA) model and the effect of maternal molecular hydrogen (H2 ) administration. We have previously demonstrated in the MIA mouse model that maternal administration of H2 attenuates oxidative damage and neuroinflammation, including induced pro-inflammatory cytokines and microglial activation, in the fetal brain. Short-term memory, sociability and social novelty, and sensorimotor gating were evaluated using the Y-maze, three-chamber, and prepulse inhibition (PPI) tests, respectively, at postnatal 3 or 4 weeks...
June 15, 2018: Scientific Reports
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