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https://www.readbyqxmd.com/read/28637049/protecting-oligodendrocytes-by-targeting-non-glutamate-receptors-as-a-new-therapeutic-strategy-for-ischemic-stroke
#1
Pan Luo, Dong Liu, Lianjun Guo
Ischemic stroke has many devastating effects within the brain. At the cellular level, excitotoxicity has been a popular pharmacological target for therapeutics. To date, many clinical trials have been performed with drugs that target excitatory neurotransmitter receptors, such as NMDA receptor agonists. The results, however, have been lackluster. Most efforts to understand the impacts of excitotoxicity on the brain have focused primarily on neurons, and to a lesser degree, on gliocytes as cellular targets. Recent evidence suggests that oligodendrocytes (OLGs), the myelin-forming cells in the central nervous system, are damaged by ischemia in a manner completely different from that in neurons...
June 21, 2017: Pharmacology
https://www.readbyqxmd.com/read/28636650/the-formation-of-lipid-droplets-favors-intracellular-mycobacterium-leprae-survival-in-sw-10-non-myelinating-schwann-cells
#2
Song-Hyo Jin, Sung-Kwan An, Seong-Beom Lee
Leprosy is a chronic infectious disease that is caused by the obligate intracellular pathogen Mycobacterium leprae (M.leprae), which is the leading cause of all non-traumatic peripheral neuropathies worldwide. Although both myelinating and non-myelinating Schwann cells are infected by M.leprae in patients with lepromatous leprosy, M.leprae preferentially invades the non-myelinating Schwann cells. However, the effect of M.leprae infection on non-myelinating Schwann cells has not been elucidated. Lipid droplets (LDs) are found in M...
June 21, 2017: PLoS Neglected Tropical Diseases
https://www.readbyqxmd.com/read/28636612/laminin-211-inhibits-protein-kinase-a-in-schwann-cells-to-modulate-neuregulin-1-type-iii-driven-myelination
#3
Monica Ghidinelli, Yannick Poitelon, Yoon Kyoung Shin, Dominique Ameroso, Courtney Williamson, Cinzia Ferri, Marta Pellegatta, Kevin Espino, Amit Mogha, Kelly Monk, Paola Podini, Carla Taveggia, Klaus-Armin Nave, Lawrence Wrabetz, Hwan Tae Park, Maria Laura Feltri
Myelin is required for proper nervous system function. Schwann cells in developing nerves depend on extrinsic signals from the axon and from the extracellular matrix to first sort and ensheathe a single axon and then myelinate it. Neuregulin 1 type III (Nrg1III) and laminin α2β1γ1 (Lm211) are the key axonal and matrix signals, respectively, but how their signaling is integrated and if each molecule controls both axonal sorting and myelination is unclear. Here, we use a series of epistasis experiments to show that Lm211 modulates neuregulin signaling to ensure the correct timing and amount of myelination...
June 2017: PLoS Biology
https://www.readbyqxmd.com/read/28634469/alexander-disease-mutations-produce-cells-with-coexpression-of-glial-fibrillary-acidic-protein-and-ng2-in-neurosphere-cultures-and-inhibit-differentiation-into-mature-oligodendrocytes
#4
Ulises Gómez-Pinedo, Maria Salomé Sirerol-Piquer, María Durán-Moreno, José Manuel García-Verdugo, Jorge Matias-Guiu
BACKGROUND: Alexander disease (AxD) is a rare disease caused by mutations in the gene encoding glial fibrillary acidic protein (GFAP). The disease is characterized by presence of GFAP aggregates in the cytoplasm of astrocytes and loss of myelin. OBJECTIVES: Determine the effect of AxD-related mutations on adult neurogenesis. METHODS: We transfected different types of mutant GFAP into neurospheres using the nucleofection technique. RESULTS: We find that mutations may cause coexpression of GFAP and NG2 in neurosphere cultures, which would inhibit the differentiation of precursors into oligodendrocytes and thus explain the myelin loss occurring in the disease...
2017: Frontiers in Neurology
https://www.readbyqxmd.com/read/28634078/astrocytes-regulate-the-expression-of-sp1r3-on-oligodendrocyte-progenitor-cells-through-cx47-and-promote-their-proliferation
#5
Dan Xu, Zhaoyu Liu, Shang Wang, Yan Peng, Xiaochuan Sun
Many degenerative diseases of the central nervous system are associated with demyelination. Oligodendrocyte progenitor cells (OPCs) are potential stem cells that can differentiate into various cell types, including oligodendrocytes (OLs). Promoting the proliferation and differentiation of OPCs into mature OLs that can myelinate axons is the key to stimulate remyelination. Here, we report that astrocytes (ASTs) increase the number of sphingosine-1-phosphate receptors 3 (S1pR3) on OPCs and promote OPCs proliferation through a direct contact via connexin 47 (Cx47)...
June 17, 2017: Biochemical and Biophysical Research Communications
https://www.readbyqxmd.com/read/28632137/electrospun-silk-polyaniline-conduits-for-functional-nerve-regeneration-in-rat-sciatic-nerve-injury-model
#6
Suradip Das, Manav Sharma, Dhiren Saharia, Kushal Sarma, Elizabeth Muir, Utpal Bora
The present study describes the fabrication of polyaniline-silk fibroin nanocomposite based nerve conduits and its subsequent implantation in a rat sciatic nerve injury model for peripheral nerve regeneration. This is the first in vivo study of polyaniline based nerve conduit describing the safety and efficacy of the conduits in treating peripheral nerve injuries. The nanocomposite was synthesised by electrospinning a mixture of silk fibroin protein and polyaniline wherein the silk nanofibers were observed to be uniformly coated with polyaniline nanoparticles...
June 20, 2017: Biomedical Materials
https://www.readbyqxmd.com/read/28632103/developmental-characteristics-of-disparate-bimanual-movement-skills-in-typically-developing-children
#7
Julian Rudisch, Jenny Butler, Hooshang Izadi, Deirdre Birtles, Dido Green
Mastery of many tasks in daily life requires role differentiated bimanual hand use with high spatiotemporal cooperation and minimal interference. The authors investigated developmental changes in the performance of a disparate bimanual movement task requiring sequenced movements. Age groups were attributed to changes in CNS structures critical for bimanual control such as the corpus callosum (CC) and the prefrontal cortex; young children (5-6 years old), older children (7-9 years old), and adolescents (10-16 years old)...
March 2, 2017: Journal of Motor Behavior
https://www.readbyqxmd.com/read/28631553/administration-of-progesterone-throughout-pregnancy-increases-maternal-steroids-without-adverse-effect-on-mature-oligodendrocyte-immunostaining-in-the-guinea-pig
#8
Julia C Shaw, Hannah K Palliser, Kerrin Palazzi, Jonathan J Hirst
Progesterone is administered to pregnant women at risk of premature labor, despite systematic reviews showing conflicting outcomes regarding its use, highlighting doubt over the effectiveness of the therapy. Progesterone can be rapidly metabolized into a number of steroids, but to date, there has been a lack of investigation into the fetal steroid profiles following administration and whether this impacts fetal neurodevelopment. The objective of this study was to determine the effect of progesterone treatment on allopregnanolone and cortisol levels in the fetus and on a marker of myelination in the fetal brain...
January 1, 2017: Reproductive Sciences
https://www.readbyqxmd.com/read/28631354/cross-population-myelination-covariance-of-human-cerebral-cortex
#9
Zhiwei Ma, Nanyin Zhang
Cross-population covariance of brain morphometric quantities provides a measure of interareal connectivity, as it is believed to be determined by the coordinated neurodevelopment of connected brain regions. Although useful, structural covariance analysis predominantly employed bulky morphological measures with mixed compartments, whereas studies of the structural covariance of any specific subdivisions such as myelin are rare. Characterizing myelination covariance is of interest, as it will reveal connectivity patterns determined by coordinated development of myeloarchitecture between brain regions...
June 20, 2017: Human Brain Mapping
https://www.readbyqxmd.com/read/28631093/myelin-regulatory-factor-drives-remyelination-in-multiple-sclerosis
#10
Greg J Duncan, Jason R Plemel, Peggy Assinck, Sohrab B Manesh, Fraser G W Muir, Ryan Hirata, Matan Berson, Jie Liu, Michael Wegner, Ben Emery, G R Wayne Moore, Wolfram Tetzlaff
Remyelination is limited in the majority of multiple sclerosis (MS) lesions despite the presence of oligodendrocyte precursor cells (OPCs) in most lesions. This observation has led to the view that a failure of OPCs to fully differentiate underlies remyelination failure. OPC differentiation requires intricate transcriptional regulation, which may be disrupted in chronic MS lesions. The expression of few transcription factors has been differentially compared between remyelinating lesions and lesions refractory to remyelination...
June 19, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28630333/boosting-cns-axon-regeneration-by-harnessing-antagonistic-effects-of-gsk3-activity
#11
Marco Leibinger, Anastasia Andreadaki, Renate Golla, Evgeny Levin, Alexander M Hilla, Heike Diekmann, Dietmar Fischer
Implications of GSK3 activity for axon regeneration are often inconsistent, if not controversial. Sustained GSK3 activity in GSK3(S/A) knock-in mice reportedly accelerates peripheral nerve regeneration via increased MAP1B phosphorylation and concomitantly reduces microtubule detyrosination. In contrast, the current study shows that lens injury-stimulated optic nerve regeneration was significantly compromised in these knock-in mice. Phosphorylation of MAP1B and CRMP2 was expectedly increased in retinal ganglion cell (RGC) axons upon enhanced GSK3 activity, but, surprisingly, no GSK3-mediated CRMP2 inhibition was detected in sciatic nerves, thus revealing a fundamental difference between central and peripheral axons...
June 19, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28629954/high-resolution-myelin-water-imaging-incorporating-local-tissue-susceptibility-analysis
#12
Zhe Wu, Hongjian He, Yi Sun, Yiping Du, Jianhui Zhong
Quantitative myelin water imaging (MWI) from signal T2* decay acquired with multiple Gradient-Recalled Echo (mGRE) sequence has been widely used since its first report. A recent study showed that with low resolution data (2mm isotropic voxels), direct application of complex fitting to a three-pool WM model with frequency shift terms could produce more stable parameter estimation for myelin water fraction mapping. MWI maps of higher spatial resolution resulting in more detailed tissue structures and reduced partial volume effects around white matter/gray matter (WM/GM) interface, however, is more desirable...
June 16, 2017: Magnetic Resonance Imaging
https://www.readbyqxmd.com/read/28629798/proteomic-analysis-of-mesenchymal-to-schwann-cell-transdifferentiation
#13
Anup D Sharma, Jayme Wiederin, Metin Uz, Pawel Ciborowski, Surya K Mallapragada, Howard E Gendelman, Donald S Sakaguchi
While transplantation of Schwann cells facilitates axon regeneration, remyelination and repair after peripheral nerve injury clinical use is limited by cell bioavailability. We posit that such limitation in cell access can be overcome by the use of autologous bone-marrow derived mesenchymal stem cells (MSCs). As MSCs can transdifferentiate to Schwann cell-phenotypes and accelerate nerve regeneration we undertook proteomic evaluation of the cells to uncover the protein contents that affects Schwann cell formulation...
June 16, 2017: Journal of Proteomics
https://www.readbyqxmd.com/read/28629387/an-updated-assessment-of-microglia-depletion-current-concepts-and-future-directions
#14
REVIEW
Jinming Han, Robert A Harris, Xing-Mei Zhang
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris...
June 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28626388/increasing-n-acetylaspartate-in-the-brain-during-postnatal-myelination-does-not-cause-the-cns-pathologies-of-canavan-disease
#15
Abhilash P Appu, John R Moffett, Peethambaran Arun, Sean Moran, Vikram Nambiar, Jishnu K S Krishnan, Narayanan Puthillathu, Aryan M A Namboodiri
Canavan disease is caused by mutations in the gene encoding aspartoacylase (ASPA), a deacetylase that catabolizes N-acetylaspartate (NAA). The precise involvement of elevated NAA in the pathogenesis of Canavan disease is an ongoing debate. In the present study, we tested the effects of elevated NAA in the brain during postnatal development. Mice were administered high doses of the hydrophobic methyl ester of NAA (M-NAA) twice daily starting on day 7 after birth. This treatment increased NAA levels in the brain to those observed in the brains of Nur7 mice, an established model of Canavan disease...
2017: Frontiers in Molecular Neuroscience
https://www.readbyqxmd.com/read/28625767/early-life-stress-perturbs-the-function-of-microglia-in-the-developing-rodent-brain-new-insights-and-future-challenges
#16
REVIEW
Frances K Johnson, Arie Kaffman
The role of the innate immune system in mediating some of the consequences of childhood abuse and neglect has received increasing attention in recent years. Most of the work to date has focused on the role that neuroinflammation plays in the long-term adult psychiatric and medical complications associated with childhood maltreatment. The effects of stress-induced neuroinflammation on neurodevelopment have received little attention because until recently this issue has not been studied systematically in animal models of early life stress...
June 15, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28624802/heparin-based-coacervate-of-bfgf-facilitates-peripheral-nerve-regeneration-by-inhibiting-endoplasmic-reticulum-stress-following-sciatic-nerve-injury
#17
Rui Li, Shuang Zou, Yanqing Wu, Yiyang Li, Sinan Khor, Yuqin Mao, Huacheng He, Ke Xu, Hongyu Zhang, Xiaokun Li, Jian Wang, Huai Jiang, Qike Jin, Qingsong Ye, Zhouguang Wang, Jian Xiao
Creating a microenvironment at the injury site that favors axonal regrowth and remyelinationis pivotal to the success of therapeutic reinnervation. The mature myelin sheath of the peripheral nervous system depends on active participation of Schwann cells to form new cytoskeletal components and tremendous amounts of relevant neurotrophic factors. In this study, we utilized a new biomaterial for growth factor delivery consisting of a biocompatible polycation, poly(ethylene argininylaspartatediglyceride) and heparin...
May 29, 2017: Oncotarget
https://www.readbyqxmd.com/read/28623948/one-carbon-metabolism-cognitive-impairment-and-csf-measures-of-alzheimer-pathology-homocysteine-and-beyond
#18
Loïc Dayon, Seu Ping Guiraud, John Corthésy, Laeticia Da Silva, Eugenia Migliavacca, Domilė Tautvydaitė, Aikaterini Oikonomidi, Barbara Moullet, Hugues Henry, Sylviane Métairon, Julien Marquis, Patrick Descombes, Sebastiano Collino, François-Pierre J Martin, Ivan Montoliu, Martin Kussmann, Jérôme Wojcik, Gene L Bowman, Julius Popp
BACKGROUND: Hyperhomocysteinemia is a risk factor for cognitive decline and dementia, including Alzheimer disease (AD). Homocysteine (Hcy) is a sulfur-containing amino acid and metabolite of the methionine pathway. The interrelated methionine, purine, and thymidylate cycles constitute the one-carbon metabolism that plays a critical role in the synthesis of DNA, neurotransmitters, phospholipids, and myelin. In this study, we tested the hypothesis that one-carbon metabolites beyond Hcy are relevant to cognitive function and cerebrospinal fluid (CSF) measures of AD pathology in older adults...
June 17, 2017: Alzheimer's Research & Therapy
https://www.readbyqxmd.com/read/28623606/marcks-is-necessary-for-oligodendrocyte-precursor-cell-maturation
#19
Zhao-Huan Zhang, Fan-Fei Ma, Hui Zhang, Xiao-Hui Xu
Oligodendrocyte precursor cell (OPC) development into myelinated oligodendrocytes demands vigorous membrane addition. Since myristoylated alanine-rich C-kinase substrate (MARCKS) reportedly contributes to Ras-associated protein (Rab)-10-associated vesicle insertion into neuronal membranes, we investigated the role of MARCKS in OPC maturation. We found that either knockdown of MARCKS or interruption of its interaction with Rab10 would cause a decrease of the cell membrane area during OPC development. Enhanced MARCKS phosphorylation by Nogo66 or myelin debris treatment inhibited OPC maturation, while its dephosphorylation by protein phosphatase 2 A activator D-erythro-sphingosine promoted OPC development in the presence of myelin debris...
June 16, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28623291/crystal-structure-of-the-dna-binding-domain-of-myelin-gene-regulatory-factor
#20
Xiangkai Zhen, Bowen Li, Fen Hu, Shufeng Yan, Gabriele Meloni, Huiliang Li, Ning Shi
Myelin-gene Regulatory Factor (MyRF) is one of the master transcription factors controlling myelin formation and development in oligodendrocytes which is crucial for the powerful brain functions. The N-terminal of MyRF, which contains a proline-rich region and a DNA binding domain (DBD), is auto-cleaved from the ER membrane, and then enters the nucleus to participate in transcription regulation of the myelin genes. Here we report the crystal structure of MyRF DBD. It shows an Ig-fold like architecture which consists of two antiparallel β-sheets with 7 main strands, packing against each other, forming a β-sandwich...
June 16, 2017: Scientific Reports
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