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Glia

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https://www.readbyqxmd.com/read/28722234/minocycline-reduces-microgliosis-and-improves-subcortical-white-matter-function-in-a-model-of-cerebral-vascular-disease
#1
Yasmina Manso, Philip R Holland, Akihiro Kitamura, Stefan Szymkowiak, Jessica Duncombe, Edel Hennessy, James L Searcy, Martina Marangoni, Andrew D Randall, Jon T Brown, Barry W McColl, Karen Horsburgh
Chronic cerebral hypoperfusion is a key mechanism associated with white matter disruption in cerebral vascular disease and dementia. In a mouse model relevant to studying cerebral vascular disease, we have previously shown that cerebral hypoperfusion disrupts axon-glial integrity and the distribution of key paranodal and internodal proteins in subcortical myelinated axons. This disruption of myelinated axons is accompanied by increased microglia and cognitive decline. The aim of the present study was to investigate whether hypoperfusion impairs the functional integrity of white matter, its relation with axon-glial integrity and microglial number, and whether by targeting microglia these effects can be improved...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28722233/cooperative-interaction-of-hepatocyte-growth-factor-and-neuregulin-regulates-schwann-cell-migration-and-proliferation-through-grb2-associated-binder-2-in-peripheral-nerve-repair
#2
Yoon Kyoung Shin, So Young Jang, Seoug Hoon Yun, Yun Young Choi, Byeol-A Yoon, Young Rae Jo, So Young Park, Min Gyoung Pak, Joo In Park, Hwan Tae Park
The sequential reactive changes in Schwann cell phenotypes in transected peripheral nerves, including dedifferentiation, proliferation and migration, are essential for nerve repair. Even though the injury-induced migratory and proliferative behaviors of Schwann cells resemble epithelial and mesenchymal transition (EMT) in tumors, the molecular mechanisms underlying this phenotypic change of Schwann cells are still unclear. Here we show that the reactive Schwann cells exhibit migratory features dependent on the expression of a scaffolding oncoprotein Grb2-associated binder-2 (Gab2), which was transcriptionally induced by neuregulin 1-ErbB2 signaling following nerve injury...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28722194/effects-of-cholesterol-transport-inhibitor-u18666a-on-app-metabolism-in-rat-primary-astrocytes
#3
Hongyan Yang, Yanlin Wang, Satyabrata Kar
Amyloid β (Aβ) peptides generated from the amyloid precursor protein (APP) play an important role in the degeneration of neurons and development of Alzheimer's disease (AD). Current evidence indicates that high levels of cholesterol-which increase the risk of developing AD-can influence Aβ production in neurons. However, it remains unclear how altered level/subcellular distribution of cholesterol in astrocytes can influence APP metabolism. In this study, we evaluated the effects of cholesterol transport inhibitor U18666A-a class II amphiphile that triggers redistribution of cholesterol within the endosomal-lysosomal (EL) system-on APP levels and metabolism in rat primary cultured astrocytes...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28722174/astrocytes-follow-ganglion-cell-axons-to-establish-an-angiogenic-template-during-retinal-development
#4
Matthew L O'Sullivan, Vanessa M Puñal, Patrick C Kerstein, Joseph A Brzezinski, Tom Glaser, Kevin M Wright, Jeremy N Kay
Immature astrocytes and blood vessels enter the developing mammalian retina at the optic nerve head and migrate peripherally to colonize the entire retinal nerve fiber layer (RNFL). Retinal vascularization is arrested in retinopathy of prematurity (ROP), a major cause of bilateral blindness in children. Despite their importance in normal development and ROP, the factors that control vascularization of the retina remain poorly understood. Because astrocytes form a reticular network that appears to provide a substrate for migrating endothelial cells, they have long been proposed to guide angiogenesis...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28707358/suppressed-oligodendrocyte-steroidogenesis-in-multiple-sclerosis-implications-for-regulation-of-neuroinflammation
#5
Roobina Boghozian, Brienne A McKenzie, Leina B Saito, Ninad Mehta, William G Branton, JianQiang Lu, Glen B Baker, Farshid Noorbakhsh, Christopher Power
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS). Neurosteroids are reported to exert anti-inflammatory effects in several neurological disorders. We investigated the expression and actions of the neurosteroid, dehydroepiandrosterone (DHEA), and its more stable 3β-sulphated ester, DHEA-S, in MS and associated experimental models. CNS tissues from patients with MS and animals with experimental autoimmune encephalomyelitis (EAE) displayed reduced DHEA concentrations, accompanied by diminished expression of the DHEA-synthesizing enzyme CYP17A1 in oligodendrocytes (ODCs), in association with increased expression of inflammatory genes including interferon (IFN)-γ and interleukin (IL)-1β...
July 14, 2017: Glia
https://www.readbyqxmd.com/read/28703353/inhibition-of-glial-hemichannels-by-boldine-treatment-reduces-neuronal-suffering-in-a-murine-model-of-alzheimer-s-disease
#6
Chenju Yi, Pascal Ezan, Paola Fernández, Julien Schmitt, Juan C Sáez, Christian Giaume, Annette Koulakoff
The contribution of reactive gliosis to the pathological phenotype of Alzheimer's disease (AD) opened the way for therapeutic strategies targeting glial cells instead of neurons. In such context, connexin hemichannels were proposed recently as potential targets since neuronal suffering is alleviated when connexin expression is genetically suppressed in astrocytes of a murine model of AD. Here, we show that boldine, an alkaloid from the boldo tree, inhibited hemichannel activity in astrocytes and microglia without affecting gap junctional communication in culture and acute hippocampal slices...
July 13, 2017: Glia
https://www.readbyqxmd.com/read/28703293/bmp-and-tgf%C3%AE-signaling-regulate-the-formation-of-m%C3%A3-ller-glia-derived-progenitor-cells-in-the-avian-retina
#7
Levi Todd, Isabella Palazzo, Natalie Squires, Ninoshka Mendonca, Andy J Fischer
Müller glia-derived progenitor cells (MGPCs) have the capability to regenerate neurons in the retinas of different vertebrate orders. The formation of MGPCs is regulated by a network of cell-signaling pathways. The purpose of this study was to investigate how BMP/Smad1/5/8- and TGFβ/Smad2/3-signaling are coordinated to influence the formation of MGPCs in the chick model system. We find that pSmad1/5/8 is selectively up-regulated in the nuclei of Müller glia following treatment with BMP4, FGF2, or NMDA-induced damage, and this up-regulation is blocked by a dorsomorphin analogue DMH1...
July 13, 2017: Glia
https://www.readbyqxmd.com/read/28699206/kiaa1199-a-novel-regulator-of-mek-erk-induced-schwann-cell-dedifferentiation
#8
Angélique Boerboom, Céline Reusch, Alexandra Pieltain, Alain Chariot, Rachelle Franzen
The molecular mechanisms that regulate Schwann cell (SC) plasticity and the role of the Nrg1/ErbB-induced MEK1/ERK1/2 signalling pathway in SC dedifferentiation or in myelination remain unclear. It is currently believed that different levels of MEK1/ERK1/2 activation define the state of SC differentiation. Thus, the identification of new regulators of MEK1/ERK1/2 signalling could help to decipher the context-specific aspects driving the effects of this pathway on SC plasticity. In this perspective, we have investigated the potential role of KIAA1199, a protein that promotes ErbB and MEK1/ERK1/2 signalling in cancer cells, in SC plasticity...
July 12, 2017: Glia
https://www.readbyqxmd.com/read/28686317/synaptotagmin-11-inhibits-cytokine-secretion-and-phagocytosis-in-microglia
#9
Cuilian Du, Yalong Wang, Feifan Zhang, Shuxin Yan, Yuan Guan, Xiaoli Gong, Ting Zhang, Xiuyu Cui, Xiaomin Wang, Claire Xi Zhang
Cytokine secretion and phagocytosis are key functions of activated microglia. However, the molecular mechanisms underlying their regulation in microglia remain largely unknown. Here, we report that synaptotagmin-11 (Syt11), a non-Ca(2+) -binding Syt implicated in Parkinson disease and schizophrenia, inhibits cytokine secretion and phagocytosis in microglia. We found Syt11 expression in microglia in brain slices and primary microglia. Interestingly, Syt11-knockdown (KD) increased cytokine secretion and NO release in primary microglia both in the absence and presence of lipopolysaccharide...
July 7, 2017: Glia
https://www.readbyqxmd.com/read/28657129/acetyl-coa-production-from-pyruvate-is-not-necessary-for-preservation-of-myelin
#10
Gustavo Della-Flora Nunes, Lauren Mueller, Nicholas Silvestri, Mulchand S Patel, Lawrence Wrabetz, M Laura Feltri, Yannick Poitelon
Oligodendrocytes and Schwann cells not only form myelin in the central and peripheral nervous system, but also provide metabolic and trophic support to the axons they ensheathe. Acetyl-CoA is potentially a key molecule in Schwann cells and oligodendrocytes because it is at the crossroads of cellular lipid biosynthesis and energy generation. The main route for acetyl-CoA production is the oxidation of pyruvate by the pyruvate dehydrogenase complex (PDC). PDC deficiency in humans results in neurodegeneration and developmental impairments in both white and gray matter structures...
June 28, 2017: Glia
https://www.readbyqxmd.com/read/28639721/trpv4-channels-contribute-to-calcium-transients-in-astrocytes-and-neurons-during-peri-infarct-depolarizations-in-a-stroke-model
#11
Cordula Rakers, Matthias Schmid, Gabor C Petzold
Stroke is one of the leading causes of death and long-term disability. In the penumbra, that is, the area surrounding the infarct core, peri-infarct depolarizations (PIDs) are accompanied by strong intracellular calcium elevations in astrocytes and neurons, thereby negatively affecting infarct size and clinical outcome. The dynamics of PIDs and the cellular pathways that are involved during PID formation and progression remain incompletely understood. We have previously shown that inositol triphosphate-gated calcium release from internal stores is a major component of PID-related astroglial calcium signals, but whether external calcium influx through membrane-localized channels also contributes to PIDs has remained unclear...
June 22, 2017: Glia
https://www.readbyqxmd.com/read/28631858/sensory-response-in-host-and-engrafted-astrocytes-of-adult-brain-in-vivo
#12
REVIEW
Kuan Zhang, Xiaowei Chen
Rapid advances in Ca(2+) imaging techniques enable us to simultaneously monitor the activities of hundreds of astrocytes in the intact brain, thus providing a powerful tool for understanding the functions of both host and engrafted astrocytes in sensory processing in vivo. These techniques include both improved Ca(2+) indicators and advanced optical recording methods. Astrocytes in multiple cortical and sub-cortical areas are able to respond to the corresponding sensory modalities. These sensory stimuli produce astrocytic Ca(2+) responses through different cellular mechanisms...
June 20, 2017: Glia
https://www.readbyqxmd.com/read/28618073/drug-discovery-for-remyelination-and-treatment-of-ms
#13
REVIEW
Katy L H Cole, Jason J Early, David A Lyons
Glia constitute the majority of the cells in our nervous system, yet there are currently no drugs that target glia for the treatment of disease. Given ongoing discoveries of the many roles of glia in numerous diseases of the nervous system, this is likely to change in years to come. Here we focus on the possibility that targeting the oligodendrocyte lineage to promote regeneration of myelin (remyelination) represents a therapeutic strategy for the treatment of the demyelinating disease multiple sclerosis, MS...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28569048/astrocyte-mediated-synapse-remodeling-in-the-pathological-brain
#14
REVIEW
Sun Kwang Kim, Junichi Nabekura, Schuichi Koizumi
Astrocytes, a major type of glia, reciprocally influence synaptic transmission and connectivity, forming the "tripartite synapses". Astrocytic metabotropic glutamate receptor (mGluR)-mediated Ca(2+) waves and release of gliotransmitters or synaptogenic molecules mediate this neuron-glia interaction in the developing brain, but this signaling has been challenged for adult brain. However, cumulative evidence has suggested that mature astrocytes exhibit re-awakening of such immature phenotype in the pathological adult brain...
June 1, 2017: Glia
https://www.readbyqxmd.com/read/28471051/a-presumed-antagonistic-lps-identifies-distinct-functional-organization-of-tlr4-in-mouse-microglia
#15
Christin Döring, Tommy Regen, Ulla Gertig, Denise van Rossum, Anne Winkler, Nasrin Saiepour, Wolfgang Brück, Uwe-Karsten Hanisch, Hana Janova
Microglia as principle innate immune cells of the central nervous system (CNS) are the first line of defense against invading pathogens. They are capable of sensing infections through diverse receptors, such as Toll-like receptor 4 (TLR4). This receptor is best known for its ability to recognize bacterial lipopolysaccharide (LPS), a causative agent of gram-negative sepsis and septic shock. A putative, naturally occurring antagonist of TLR4 derives from the photosynthetic bacterium Rhodobacter sphaeroides. However, the antagonistic potential of R...
May 4, 2017: Glia
https://www.readbyqxmd.com/read/28456012/neuregulin-1-positively-modulates-glial-response-and-improves-neurological-recovery-following-traumatic-spinal-cord-injury
#16
Arsalan Alizadeh, Scott M Dyck, Hardeep Kataria, Ghazaleh M Shahriary, Dung H Nguyen, Kallivalappil T Santhosh, Soheila Karimi-Abdolrezaee
Spinal cord injury (SCI) results in glial activation and neuroinflammation, which play pivotal roles in the secondary injury mechanisms with both pro- and antiregeneration effects. Presently, little is known about the endogenous molecular mechanisms that regulate glial functions in the injured spinal cord. We previously reported that the expression of neuregulin-1 (Nrg-1) is acutely and chronically declined following traumatic SCI. Here, we investigated the potential ramifications of Nrg-1 dysregulation on glial and immune cell reactivity following SCI...
April 29, 2017: Glia
https://www.readbyqxmd.com/read/28456003/sodium-dependent-vitamin-c-transporter-2-deficiency-impairs-myelination-and-remyelination-after-injury-roles-of-collagen-and-demethylation
#17
Dominik Röhr, Hartmut Halfter, Jörg B Schulz, Peter Young, Burkhard Gess
Peripheral nerve myelination involves rapid production of tightly bound lipid layers requiring cholesterol biosynthesis and myelin protein expression, but also a collagen-containing extracellular matrix providing mechanical stability. In previous studies, we showed a function of ascorbic acid in peripheral nerve myelination and extracellular matrix formation in adult mice. Here, we sought the mechanism of action of ascorbic acid in peripheral nerve myelination using different paradigms of myelination in vivo and in vitro...
April 29, 2017: Glia
https://www.readbyqxmd.com/read/28636132/trpc1-and-trpc3-dependent-ca-2-signaling-in-mouse-cortical-astrocytes-affects-injury-evoked-astrogliosis-in-vivo
#18
Thabet Belkacemi, Alexander Niermann, Laura Hofmann, Ulrich Wissenbach, Lutz Birnbaumer, Petra Leidinger, Christina Backes, Eckart Meese, Andreas Keller, Xianshu Bai, Anja Scheller, Frank Kirchhoff, Stephan E Philipp, Petra Weissgerber, Veit Flockerzi, Andreas Beck
Following brain injury astrocytes change into a reactive state, proliferate and grow into the site of lesion, a process called astrogliosis, initiated and regulated by changes in cytoplasmic Ca(2+) . Transient receptor potential canonical (TRPC) channels may contribute to Ca(2+) influx but their presence and possible function in astrocytes is not known. By RT-PCR and RNA sequencing we identified transcripts of Trpc1, Trpc2, Trpc3, and Trpc4 in FACS-sorted glutamate aspartate transporter (GLAST)-positive cultured mouse cortical astrocytes and subcloned full-length Trpc1 and Trpc3 cDNAs from these cells...
September 2017: Glia
https://www.readbyqxmd.com/read/28618115/iron-sulfur-glutaredoxin-2-protects-oligodendrocytes-against-damage-induced-by-nitric-oxide-release-from-activated-microglia
#19
Klaudia Lepka, Katrin Volbracht, Eckhard Bill, Reiner Schneider, Natalia Rios, Thomas Hildebrandt, Jens Ingwersen, Timur Prozorovski, Christopher Horst Lillig, Jack van Horssen, Lawrence Steinman, Hans-Peter Hartung, Rafael Radi, Arne Holmgren, Orhan Aktas, Carsten Berndt
Demyelinated brain lesions, a hallmark of autoimmune neuroinflammatory diseases like multiple sclerosis, result from oligodendroglial cell damage. Activated microglia are considered a major source of nitric oxide and subsequent peroxynitrite-mediated damage of myelin. Here, we provide biochemical and biophysical evidence that the oxidoreductase glutaredoxin 2 inhibits peroxynitrite formation by transforming nitric oxide into dinitrosyl-diglutathionyl-iron-complexes. Glutaredoxin 2 levels influence both survival rates of primary oligodendrocyte progenitor cells and preservation of myelin structure in cerebellar organotypic slice cultures challenged with activated microglia or nitric oxide donors...
September 2017: Glia
https://www.readbyqxmd.com/read/28618077/generation-of-a-microglial-developmental-index-in-mice-and-in-humans-reveals-a-sex-difference-in-maturation-and-immune-reactivity
#20
Richa Hanamsagar, Mark D Alter, Carina S Block, Haley Sullivan, Jessica L Bolton, Staci D Bilbo
Evidence suggests many neurological disorders emerge when normal neurodevelopmental trajectories are disrupted, i.e., when circuits or cells do not reach their fully mature state. Microglia play a critical role in normal neurodevelopment and are hypothesized to contribute to brain disease. We used whole transcriptome profiling with Next Generation sequencing of purified developing microglia to identify a microglial developmental gene expression program involving thousands of genes whose expression levels change monotonically (up or down) across development...
September 2017: Glia
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