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https://www.readbyqxmd.com/read/28214987/severe-convulsions-and-dysmyelination-in-both-jimpy-and-cx32-47-mice-may-associate-astrocytic-l-channel-function-with-myelination-and-oligodendrocytic-connexins-with-internodal-kv-channels
#1
Y H Gerald Chaban, Ye Chen, Elna Hertz, Leif Hertz
The Jimpy mouse illustrates the importance of interactions between astrocytes and oligodendrocytes. It has a mutation in Plp coding for proteolipid protein and DM20. Its behavior is normal at birth but from the age of ~2 weeks it shows severe convulsions associated with oligodendrocyte/myelination deficits and early death. A normally occurring increase in oxygen consumption by highly elevated K(+) concentrations is absent in Jimpy brain slices and cultured astrocytes, reflecting that Plp at early embryonic stages affects common precursors as also shown by the ability of conditioned medium from normal astrocytes to counteract histological abnormalities...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28214986/astrocyte-sodium-signalling-and-panglial-spread-of-sodium-signals-in-brain-white-matter
#2
Behrouz Moshrefi-Ravasdjani, Evelyn L Hammel, Karl W Kafitz, Christine R Rose
In brain grey matter, excitatory synaptic transmission activates glutamate uptake into astrocytes, inducing sodium signals which propagate into neighboring astrocytes through gap junctions. These sodium signals have been suggested to serve an important role in neuro-metabolic coupling. So far, it is unknown if astrocytes in white matter-that is in brain regions devoid of synapses-are also able to undergo such intra- and intercellular sodium signalling. In the present study, we have addressed this question by performing quantitative sodium imaging in acute tissue slices of mouse corpus callosum...
February 18, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28214347/involvement-of-the-guanine-nucleotide-exchange-factor-vav3-in-central-nervous-system-development-and-plasticity
#3
Annika Ulc, Christine Gottschling, Ina Schäfer, David Wegrzyn, Simon van Leeuwen, Veronika Luft, Jacqueline Reinhard, Andreas Faissner
Small GTP-hydrolysing enzymes (GTPases) of the RhoA family play manifold roles in cell biology and are regulated by upstream guanine nucleotide exchange factors (GEFs). Herein, we focus on the GEFs of the Vav subfamily. Vav1 was originally described as a protooncogene of the hematopoietic lineage. The GEFs Vav2 and Vav3 are more broadly expressed in various tissues. In particular, the GEF Vav3 may play important roles in the developing nervous system during the differentiation of neural stem cells into the major lineages, namely neurons, oligodendrocytes and astrocytes...
February 18, 2017: Biological Chemistry
https://www.readbyqxmd.com/read/28213969/highly-efficient-neural-conversion-of-human-pluripotent-stem-cells-in-adherent-and-animal-free-conditions
#4
Dunja Lukovic, Andrea Diez Lloret, Petra Stojkovic, Daniel Rodríguez-Martínez, Maria Amparo Perez Arago, Francisco Javier Rodriguez-Jimenez, Patricia González-Rodríguez, José López-Barneo, Eva Sykova, Pavla Jendelova, Jelena Kostic, Victoria Moreno-Manzano, Miodrag Stojkovic, Shomi S Bhattacharya, Slaven Erceg
Neural differentiation of human embryonic stem cells (hESCs) and induced pluripotent stem cells (hiPSCs) can produce a valuable and robust source of human neural cell subtypes, holding great promise for the study of neurogenesis and development, and for treating neurological diseases. However, current hESCs and hiPSCs neural differentiation protocols require either animal factors or embryoid body formation, which decreases efficiency and yield, and strongly limits medical applications. Here we develop a simple, animal-free protocol for neural conversion of both hESCs and hiPSCs in adherent culture conditions...
February 18, 2017: Stem Cells Translational Medicine
https://www.readbyqxmd.com/read/28213437/%C3%AE-synuclein-multiple-system-atrophy-prions
#5
Amanda L Woerman, Joel C Watts, Atsushi Aoyagi, Kurt Giles, Lefkos T Middleton, Stanley B Prusiner
Multiple system atrophy (MSA) is a rapidly progressive neurodegenerative disease arising from the misfolding and accumulation of the protein α-synuclein in oligodendrocytes, where it forms glial cytoplasmic inclusions (GCIs). Several years of studying synthetic α-synuclein fibrils has provided critical insight into the ability of α-synuclein to template endogenous protein misfolding, giving rise to fibrillar structures capable of propagating from cell to cell. However, more recent studies with MSA-derived α-synuclein aggregates have shown that they have a similar ability to undergo template-directed propagation, like PrP prions...
February 17, 2017: Cold Spring Harbor Perspectives in Medicine
https://www.readbyqxmd.com/read/28212538/sevoflurane-preconditioning-induced-endogenous-neurogenesis-against-ischemic-brain-injury-by-promoting-microglial-activation
#6
Li Li, Hexige Saiyin, Jingmo Xie, Lixiang Ma, Lei Xue, Wei Wang, Weimin Liang, Qiong Yu
Brain ischemia causes irreversible damage to functional neurons in cases of infarct. Promoting endogenous neurogenesis to replace necrotic neurons is a promising therapeutic strategy for ischemia patients. The neuroprotective role of sevoflurane preconditioning implies that it might also enhance endogenous neurogenesis and functional restoration in the infarct region. By using a transient middle cerebral artery occlusion (tMCAO) model, we discovered that endogenous neurogenesis was enhanced by sevoflurane preconditioning...
February 14, 2017: Oncotarget
https://www.readbyqxmd.com/read/28205591/protective-effect-of-17%C3%AE-estradiol-upon-hippocampal-spine-density-and-cognitive-function-in-an-animal-model-of-vascular-dementia
#7
Ying Zhu, Quanguang Zhang, Wenli Zhang, Ning Li, Yongxin Dai, Jingyi Tu, Fang Yang, Darrell W Brann, Ruimin Wang
The current study examined whether the steroid hormone, 17β-estradiol (E2) can exert long-lasting beneficial effects upon axonal health, synaptic plasticity, dementia-related amyloid-beta (Aβ) protein expression, and hippocampal-dependent cognitive function in an animal model of chronic cerebral hypoperfusion and vascular dementia (VaD). Chronic cerebral hypoperfusion and VaD was induced by bilateral common carotid artery occlusion (BCCAO) in adult male Sprague Dawley rats. Low dose E2 administered for the first 3-months after BCCAO exerted long-lasting beneficial effects, including significant neuroprotection of hippocampal CA1 neurons and preservation of hippocampal-dependent cognitive function when examined at 6-months after BCCAO...
February 16, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28203606/dna-methylation-in-oligodendroglial-cells-during-developmental-myelination-and-in-disease
#8
Sarah Moyon, Patrizia Casaccia
Oligodendrocyte progenitor cells (OPC) are the myelinating cells of the central nervous system (CNS). During development, they differentiate into mature oligodendrocytes (OL) and ensheath axons, providing trophic and functional support to the neurons. This process is regulated by the dynamic expression of specific transcription factors, which, in turn, is controlled by epigenetic marks such as DNA methylation. Here we discuss recent findings showing that DNA methylation levels are differentially regulated in the oligodendrocyte lineage during developmental myelination, affecting both genes expression and alternative splicing events...
2017: Neurogenesis (Austin, Tex.)
https://www.readbyqxmd.com/read/28202749/endothelial-cell-oligodendrocyte-interactions-in-small-vessel-disease-and-aging
#9
REVIEW
Rikesh M Rajani, Anna Williams
Cerebral small vessel disease (SVD) is a prevalent, neurological disease that significantly increases the risk of stroke and dementia. The main pathological changes are vascular, in the form of lipohyalinosis and arteriosclerosis, and in the white matter (WM), in the form of WM lesions. Despite this, it is unclear to what extent the key cell types involved-the endothelial cells (ECs) of the vasculature and the oligodendrocytes of the WM-interact. Here, we describe the work that has so far been carried out suggesting an interaction between ECs and oligodendrocytes in SVD...
March 1, 2017: Clinical Science (1979-)
https://www.readbyqxmd.com/read/28202388/viral-vector-reprogramming-of-adult-resident-striatal-oligodendrocytes-into-functional-neurons
#10
Marc S Weinberg, Hugh E Criswell, Sara K Powell, Aadra P Bhatt, Thomas J McCown
Recent advances suggest that in vivo reprogramming of endogenous cell populations provides a viable alternative for neuron replacement. Astrocytes and oligodendrocyte precursor cells can be induced to transdifferentiate into neurons in the CNS, but, in these instances, reprogramming requires either transgenic mice or retroviral-mediated gene expression. We developed a microRNA (miRNA)-GFP construct that in vitro significantly reduced the expression of polypyrimidine tract-binding protein, and, subsequently, we packaged this construct in a novel oligodendrocyte preferring adeno-associated virus vector...
February 12, 2017: Molecular Therapy: the Journal of the American Society of Gene Therapy
https://www.readbyqxmd.com/read/28196893/phosphorylation-of-%C3%AE-b-crystallin-supports-reactive-astrogliosis-in-demyelination
#11
Hedwich F Kuipers, Jane Yoon, Jack van Horssen, May H Han, Paul L Bollyky, Theo D Palmer, Lawrence Steinman
The small heat shock protein αB-crystallin (CRYAB) has been implicated in multiple sclerosis (MS) pathogenesis. Earlier studies have indicated that CRYAB inhibits inflammation and attenuates clinical disease when administered in the experimental autoimmune encephalomyelitis model of MS. In this study, we evaluated the role of CRYAB in primary demyelinating events. Using the cuprizone model of demyelination, a noninflammatory model that allows the analysis of glial responses in MS, we show that endogenous CRYAB expression is associated with increased severity of demyelination...
February 14, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28196689/subependymal-zone-derived-oligodendroblasts-respond-to-focal-demyelination-but-fail-to-generate-myelin-in-young-and-aged-mice
#12
Ilias Kazanis, Kimberley A Evans, Evangelia Andreopoulou, Christina Dimitriou, Christos Koutsakis, Ragnhildur Thora Karadottir, Robin J M Franklin
Two populations of oligodendrogenic progenitors co-exist within the corpus callosum (CC) of the adult mouse. Local, parenchymal oligodendrocyte progenitor cells (pOPCs) and progenitors generated in the subependymal zone (SEZ) cytogenic niche. pOPCs are committed perinatally and retain their numbers through self-renewing divisions, while SEZ-derived cells are relatively "young," being constantly born from neural stem cells. We compared the behavior of these populations, labeling SEZ-derived cells using hGFAP:Cre(Ert2) mice, within the homeostatic and regenerating CC of the young-adult and aging brain...
February 8, 2017: Stem Cell Reports
https://www.readbyqxmd.com/read/28195192/ng2-glial-cells-regulate-neuroimmunological-responses-to-maintain-neuronal-function-and-survival
#13
Masayuki Nakano, Yasuhisa Tamura, Masanori Yamato, Satoshi Kume, Asami Eguchi, Kumi Takata, Yasuyoshi Watanabe, Yosky Kataoka
NG2-expressing neural progenitor cells (i.e., NG2 glial cells) maintain their proliferative and migratory activities even in the adult mammalian central nervous system (CNS) and produce myelinating oligodendrocytes and astrocytes. Although NG2 glial cells have been observed in close proximity to neuronal cell bodies in order to receive synaptic inputs, substantive non-proliferative roles of NG2 glial cells in the adult CNS remain unclear. In the present study, we generated NG2-HSVtk transgenic rats and selectively ablated NG2 glial cells in the adult CNS...
February 14, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28194442/redirecting-n-acetylaspartate-metabolism-in-the-central-nervous-system-normalizes-myelination-and-rescues-canavan-disease
#14
Dominic J Gessler, Danning Li, Hongxia Xu, Qin Su, Julio Sanmiguel, Serafettin Tuncer, Constance Moore, Jean King, Reuben Matalon, Guangping Gao
Canavan disease (CD) is a debilitating and lethal leukodystrophy caused by mutations in the aspartoacylase (ASPA) gene and the resulting defect in N-acetylaspartate (NAA) metabolism in the CNS and peripheral tissues. Recombinant adeno-associated virus (rAAV) has the ability to cross the blood-brain barrier and widely transduce the CNS. We developed a rAAV-based and optimized gene replacement therapy, which achieves early, complete, and sustained rescue of the lethal disease phenotype in CD mice. Our treatment results in a super-mouse phenotype, increasing motor performance of treated CD mice beyond that of WT control mice...
February 9, 2017: JCI Insight
https://www.readbyqxmd.com/read/28193690/lingo-1-regulates-oligodendrocyte-differentiation-through-the-cytoplasmic-gelsolin-signaling-pathway
#15
Zhaohui Shao, Xinhua Lee, Guanrong Huang, Guoqing Sheng, Christopher E Henderson, Daniel Louvard, Jiho Sohn, Blake Pepinsky, Sha Mi
Differentiation and maturation of oligodendrocyte progenitor cells (OPCs) involve the assembly and disassembly of actin microfilaments. How actin dynamics is regulated during this process remains poorly understood. Leucine rich repeat and Immunoglobulin-like domain-containing Nogo receptor interacting protein 1(LINGO-1) is a negative regulator of OPC differentiation. We discovered that anti-LINGO-1 antibody promoted OPC differentiation was accompanied by upregulation of cytoplasmic gelsolin (cGSN), an abundant actin-severing protein involved in the depolymerization of actin filaments...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28193689/signaling-by-fgf-receptor-2-not-fgf-receptor-1-regulates-myelin-thickness-through-activation-of-erk1-2-mapk-which-promotes-mtorc1-activity-in-an-akt-independent-manner
#16
M Furusho, A Ishii, R Bansal
FGF signaling has emerged as a significant 'late-stage' regulator of myelin thickness in the CNS, independent of oligodendrocyte differentiation. Therefore, it is critically important to identify the specific FGF-Receptor-type and its downstream signaling molecules in oligodendrocytes to obtain better insights into the regulatory mechanisms of myelin growth. Here, we show that FGF-Receptor-type-2 (FGFR2) is highly enriched at the paranodal loops of myelin. Conditional ablation of this receptor-type, but not FGF-Receptor-type-1 (FGFR1), resulted in attenuation of myelin growth, expression of major myelin genes, key transcription factor Myrf and ERK1/2 activity...
February 13, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28192611/deficiency-of-trek-1-potassium-channel-exacerbates-secondary-injury-following-spinal-cord-injury-in-mice
#17
Yongkang Fang, Xiaojiang Huang, Yue Wan, Hao Tian, Yeye Tian, Wei Wang, Suiqiang Zhu, Minjie Xie
Spinal cord injury (SCI) involves complex pathological process which can be complicated by secondary injury. TREK-1 is a member of the two-pore domain potassium (K2P) channel family, which can be modulated by a number of physiological and pathological stimuli. Recent studies suggest that TREK-1 plays an active role in depression, pain and neuroprotection. However, its role in the pathological process after SCI remains unclear. In this study, we tested the expression and function of TREK-1 in spinal cord of mice after traumatic SCI...
February 13, 2017: Journal of Neurochemistry
https://www.readbyqxmd.com/read/28192470/differentiation-of-oligodendrocyte-progenitor-cells-from-dissociated-monolayer-and-feeder-free-cultured-pluripotent-stem-cells
#18
Tomoko Yamashita, Yuki Miyamoto, Yoshio Bando, Takashi Ono, Sakurako Kobayashi, Ayano Doi, Toshihiro Araki, Yosuke Kato, Takayuki Shirakawa, Yutaka Suzuki, Junji Yamauchi, Shigetaka Yoshida, Naoya Sato
Oligodendrocytes myelinate axons and form myelin sheaths in the central nervous system. The development of therapies for demyelinating diseases, including multiple sclerosis and leukodystrophies, is a challenge because the pathogenic mechanisms of disease remain poorly understood. Primate pluripotent stem cell-derived oligodendrocytes are expected to help elucidate the molecular pathogenesis of these diseases. Oligodendrocytes have been successfully differentiated from human pluripotent stem cells. However, it is challenging to prepare large amounts of oligodendrocytes over a short amount of time because of manipulation difficulties under conventional primate pluripotent stem cell culture methods...
2017: PloS One
https://www.readbyqxmd.com/read/28188847/pharmacological-inhibition-of-spinal-cord-injury-stimulated-ribosomal-biogenesis-does-not-affect-locomotor-outcome
#19
Ewa Kilanczyk, Kariena R Andres, Justin Hallgren, Sujata Saraswat Ohri, Marikki Laiho, Scott R Whittemore, Michal Hetman
After unresolved endoplasmic reticulum stress, recovery of protein synthesis including increased expression of ribosomal components and translation factors may induce cell death. Using a mouse model of moderate contusive spinal cord injury (SCI) at the T9 level, upregulation of ribosomal biogenesis was observed in the injury epicenter at 24h after trauma. Such upregulation coincided with endoplasmic reticulum stress response as previously reported in this model. It was also accompanied by changes in expression of many other genes associated with translational regulation...
February 7, 2017: Neuroscience Letters
https://www.readbyqxmd.com/read/28188285/rna-binding-protein-quaking-stabilizes-sirt2-mrna-during-oligodendroglial-differentiation
#20
Merlin P Thangaraj, Kendra L Furber, Jotham K Gan, Shaoping Ji, Larhonda Sobchishin, J Ronald Doucette, Adil J Nazarali
Myelination is controlled by timely expression of genes involved in the differentiation of oligodendrocyte precursor cells (OPCs) into myelinating oligodendrocytes (OLs). Sirtuin 2 (SIRT2), a NAD+-dependent deacetylase, plays a critical role in OL differentiation by promoting both arborization and downstream expression of myelin specific genes. However, the mechanisms involved in regulating SIRT2 expression during OL development are largely unknown. The RNA binding protein Quaking (QKI) plays an important role in myelination by post-transcriptionally regulating the expression of several myelin specific genes...
February 10, 2017: Journal of Biological Chemistry
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