The formation of a glial scar does not prohibit remyelination in an animal model of multiple sclerosis
In the demyelinating scenario of MOG EAE in the DA rat the astroglial reaction does not impede plaque repair. A finely regulated expression of astrocytic factors is necessary to promote OPC guidance, migration, differentiation, and survival. AbstractThe role of astrocytes in the pathophysiology of multiple sclerosis (MS) is discussed controversially. Especially the formation of the glial scar is often believed to act as a barrier for remyelination. At the same time, astrocytes are known to produce factors that influence oligodendrocyte precursor cell (OPC) survival. To explore these mechanisms, we investigated the astrocyt...
Source: Glia - November 28, 2018 Category: Neurology Authors: Michaela Tanja Haindl, Ulrike K öck, Milena Zeitelhofer‐Adzemovic, Franz Fazekas, Sonja Hochmeister Tags: RESEARCH ARTICLE Source Type: research

Morphological profile determines the frequency of spontaneous calcium events in astrocytic processes
Majority of spontaneous Ca2+ events start in thin astrocytic processes Higher surface ‐to‐volume ratio of the process is responsible for larger intracellular Ca2+ fluctuations Larger intracellular Ca2+ fluctuations trigger Ca2+‐dependent Ca2+ release AbstractAstrocytes express a complex repertoire of intracellular Ca2+ transients (events) that represent a major form of signaling within individual cells and in astrocytic syncytium. These events have different spatiotemporal profiles, which are modulated by neuronal activity. Spontaneous Ca2+ events appear more frequently in distal astrocytic processes and independentl...
Source: Glia - November 22, 2018 Category: Neurology Authors: Yu ‐Wei Wu, Susan Gordleeva, Xiaofang Tang, Pei‐Yu Shih, Yulia Dembitskaya, Alexey Semyanov Tags: RESEARCH ARTICLE Source Type: research

Targeting microglia attenuates neuroinflammation ‐related neural damage in mice carrying human PLP1 mutations
Main PointsTreatment ofPLPmut mice with PLX3397 (150  ppm in chow)• depletes microglia of the CNS;• reduces neuroinflammation by T‐lymphocytes;• attenuates axon and myelin degeneration, neuron loss, and retinal thinning. AbstractGenetically caused neurological disorders of the central nervous system (CNS) usually result in poor or even fatal clinical outcome and few or no causative treatments are available. Often, these disorders are associated with disease ‐amplifying neuroinflammation, a feature shared by progressive forms of multiple sclerosis (PMS), another poorly treatable disorder of the CNS. We hav...
Source: Glia - November 22, 2018 Category: Neurology Authors: Janos Groh, Dennis Klein, Kristina Berve, Brian L. West, Rudolf Martini Tags: RESEARCH ARTICLE Source Type: research

Region ‐specific control of microglia by adenosine A2A receptors: uncoupling anxiety and associated cognitive deficits in female rats
We report that iuDEX impaired recognition memory and deteriorated neuronal synchronization between mPFC and dHIP. These functional deficits are paralleled by microglia hyper ‐ramification in the dHIP and decreased ramification in the mPFC, showing a heterogeneous remodeling of microglia morphology, both postnatally and at adulthood in different brain regions, that differently affect mood and cognition. The chronic blockade of adenosine A2A receptors (A2AR), which are core regulators of microglia morphology and physiology, ameliorated the cognitive deficits, but not the anxiety ‐like behavior. Notably, A2AR blockade rec...
Source: Glia - November 21, 2018 Category: Neurology Authors: Joana Mendes Duarte, Rita Gaspar, Liliana Caetano, Patr ícia Patrício, Carina Soares‐Cunha, António Mateus‐Pinheiro, Nuno Dinis Alves, Ana Rita Santos, Samira G Ferreira, Vanessa Sardinha, João Filipe Oliveira, Carlos Fontes‐Ribeiro, Tags: RESEARCH ARTICLE Source Type: research

Reactive astrocytes in multiple sclerosis impair neuronal outgrowth through TRPM7 ‐mediated chondroitin sulfate proteoglycan production
Main Points TRPM7 is highly expressed in reactive astrocytes within MS lesions. Enhanced astrocytic TRPM7 levels impair neurite outgrowth by increased production of chondroitin sulfate proteoglycans, a key component of the gliotic scar. AbstractMultiple sclerosis (MS) is a chronic inflammatory disorder of the central nervous system (CNS), characterized by inflammation ‐mediated demyelination, axonal injury and neurodegeneration. The mechanisms underlying impaired neuronal function are not fully understood, but evidence is accumulating that the presence of the gliotic scar produced by reactive astrocytes play a critical r...
Source: Glia - November 19, 2018 Category: Neurology Authors: Alwin Kamermans, Kirsten E. Planting, Kees Jalink, Jack van Horssen, Helga E. de Vries Tags: RESEARCH ARTICLE Source Type: research

Unique role for dentate gyrus microglia in neuroblast survival and in VEGF ‐induced activation
Main Points Dentate gyrus microglia are a unique subpopulation which support neuroblasts survival. Dentate gyrus microglia are characterized by a unique set of genes and by being selectively reactive in response to the angiogenic and neurogenic factor VEGF. AbstractNeurogenic roles of microglia (MG) are thought to include an active role in adult hippocampal neurogenesis in addition to their established roles in pruning surplus dendrites and clearing dead neuroblasts. However, identification of such a role and its delineation in the neurogenic cascade is yet to be established. Using diphtheria toxin ‐aided MG ablation, w...
Source: Glia - November 19, 2018 Category: Neurology Authors: Tirzah Kreisel, Brachi Wolf, Eli Keshet, Tamar Licht Tags: RESEARCH ARTICLE Source Type: research

PPAR β/δ‐agonist GW0742 ameliorates dysfunction in fatty acid oxidation in PSEN1ΔE9 astrocytes
Alzheimer's disease mutation PSEN1 ΔE9 causes impaired fatty acid oxidation in human and murine astrocytes. The deficit is rescued by activation of PPARβ/δ with an agonist, GW0742. GW0742 also improves cognitive deficits of APP/PS1 mice. AbstractAstrocytes are the gatekeepers of neuronal energy supply. In neurodegenerative diseases, bioenergetics demand increases and becomes reliant upon fatty acid oxidation as a source of energy. Defective fatty acid oxidation and mitochondrial dysfunctions correlate with hippocampal neurodegeneration and memory deficits in Alzheimer's disease (AD), but it is unclear whether energy met...
Source: Glia - November 19, 2018 Category: Neurology Authors: Henna Konttinen, Irina Gureviciene, Minna Oksanen, Alexandra Grubman, Sanna Loppi, Mikko T. Huuskonen, Paula Korhonen, Riikka Lampinen, Meike Keuters, Irina Belaya, Heikki Tanila, Katja M. Kanninen, Gundars Goldsteins, Gary Landreth, Jari Ko Tags: RESEARCH ARTICLE Source Type: research

Microglial modulation through colony ‐stimulating factor‐1 receptor inhibition attenuates demyelination
Main Points• CSF‐1R inhibitor BLZ945 reduces the number of microglial cells• BLZ945 reduces myelin damage in acute CPZ‐induced demyelination mainly in myelin‐poor areas• BLZ945 promotes remyelination and neuroprotection in chronic CPZ‐induced demyelination AbstractMultiple sclerosis (MS) is one of the most common causes of progressive disability affecting young people with very few therapeutic options available for its progressive forms. Its pathophysiology involves demyelination and neurodegeneration apparently driven by microglial activation, which is physiologically dependent on colony ‐stimulating...
Source: Glia - November 19, 2018 Category: Neurology Authors: Victoria Sof ía Berenice Wies Mancini, Juana María Pasquini, Jorge Daniel Correale, Laura Andrea Pasquini Tags: RESEARCH ARTICLE Source Type: research

The guanine nucleotide exchange factor Vav3 modulates oligodendrocyte precursor differentiation and supports remyelination in white matter lesions
Main Points Vav3−/− oligodendrocytes (OLs) show accelerated maturation Vav3−/− OLs posses impaired myelination and remyelination potency in vitro Vav3−/− mice display reduced remyelination in vivo Vav3−/− OLs present changed activation levels of Rho GTPases AbstractThe tightly controlled processes of myelination and remyelination require the participation of the cytoskeleton. The reorganization of the cytoskeleton is controlled by small GTPases of the RhoA family. Here, we report that Vav3, a Rho GTPase regulating guanine nucleotide exchange factor (GEF) is involved in oligodendrocyte maturation, myelinatio...
Source: Glia - November 18, 2018 Category: Neurology Authors: Annika Ulc, Andre Zeug, Juliane Bauch, Simon Leeuwen, Tanja Kuhlmann, Charles ffrench ‐Constant, Evgeni Ponimaskin, Andreas Faissner Tags: RESEARCH ARTICLE Source Type: research

Issue Information ‐ Table of Contents
Glia, Volume 66, Issue 10, Page 2041-2043, October 2018. (Source: Glia)
Source: Glia - November 17, 2018 Category: Neurology Tags: ISSUE INFORMATION ‐ TABLE OF CONTENTS Source Type: research

Helper CD4 T cells expressing granzyme B cause glial fibrillary acidic protein fragmentation in astrocytes in an MHCII ‐independent manner
Main Points • Helper T cells released granzyme B upon contact with cultured human astrocytes in an MHCII‐independent manner.• Helper T cells caused GFAP fragmentation in a granzyme B and caspase‐dependent manner.• Sublethally injured astrocytes were not apoptotic but had a reduced ability to migrate a nd to support oligodendrocytes. AbstractDuring inflammatory processes of the central nervous system, helper T cells have the capacity to cross the blood –brain barrier and injure or kill neural cells through cytotoxic mechanisms. Glial fibrillary acidic protein (GFAP) is an intermediate filament protein that is pa...
Source: Glia - November 16, 2018 Category: Neurology Authors: Brandon Stopnicki, Manon Blain, Qiao ‐Ling Cui, Timothy E. Kennedy, Jack P. Antel, Luke M. Healy, Peter J. Darlington Tags: RESEARCH ARTICLE Source Type: research

Interaction between microglia and retinal pigment epithelial cells determines the integrity of outer blood ‐retinal barrier in diabetic retinopathy
In this study, we aimed to investigate the mechanisms of the outer BRB disruption regarding the interaction between RPE an d microglia. In mice with high‐fat diet‐induced obesity and streptozotocin‐induced hyperglycemia, microglia accumulated on the RPE layer, as in those after intravitreal injection of interleukin (IL)‐6, which is elevated in ocular fluids of patients with diabetic retinopathy. Although IL‐6 did not directly affect the levels of zonula occludens (ZO)‐1 and occludin in RPE cells, IL‐6 increasedVEGFA mRNA in RPE cells to recruit microglial cells. In microglial cells, IL ‐6 upregulated the mR...
Source: Glia - November 16, 2018 Category: Neurology Authors: Dong Hyun Jo, Jang ‐Hyuk Yun, Chang Sik Cho, Jin Hyoung Kim, Jeong Hun Kim, Chung‐Hyun Cho Tags: RESEARCH ARTICLE Source Type: research

Dedifferentiated Schwann cells secrete progranulin that enhances the survival and axon growth of motor neurons
Main Points Schwann cells (SCs) express and secrete progranulin (PGRN), depending on the differentiation status of SCs PGRN expression markedly increases as SCs undergo dedifferentiation both in culture and in vivo PGRN secreted from SCs enhances the survival and axon growth of motor neurons AbstractSchwann cells (SCs), the primary glia in the peripheral nervous system (PNS), display remarkable plasticity in that fully mature SCs undergo dedifferentiation and convert to repair SCs upon nerve injury. Dedifferentiated SCs provide essential support for PNS regeneration by producing signals that enhance the survival and axon r...
Source: Glia - November 15, 2018 Category: Neurology Authors: Sujin Hyung, Sun ‐Kyoung Im, Bo Yoon Lee, Jihye Shin, Jong‐Chul Park, Cheolju Lee, Jun‐Kyo Francis Suh, Eun‐Mi Hur Tags: RESEARCH ARTICLE Source Type: research

Drosophila glia: Few cell types and many conserved functions
• Many glial functions are evolutionarily conserved• Drosophila has six functionally distinct glial subtypes, including one PNS specific form• Drosophila glia can be used to model human diseases AbstractGlial cells constitute without any dispute an essential element in providing an efficiently operating nervous system. Work in many labs over the last decades has demonstrated that neuronal function, from action potential generation to its propagation, from eliciting synaptic responses to the subsequent postsynaptic integration, is evolutionarily highly conserved. Likewise, the biology of glial cells appears conserved ...
Source: Glia - November 15, 2018 Category: Neurology Authors: Kerem Yildirim, Johanna Petri, Rita Kottmeier, Christian Kl ämbt Tags: REVIEW ARTICLE Source Type: research

Rescuing the negative impact of human endogenous retrovirus envelope protein on oligodendroglial differentiation and myelination
p57kip2 and ENV act as oligodendroglial inhibitors p57kip2 binds V ‐ATPase providing an interface with ENV‐triggered pathway Anti‐ENV antibody and molecular/pharmacological neutralization of p57kip2/V‐ATPase rescues myelination in presence of ENV AbstractRemyelination in the adult CNS depends on activation, differentiation, and functional integration of resident oligodendroglial precursor cells (OPCs) and constitutes the only spontaneous neuroregenerative process able to compensate for functional deficits upon loss of oligodendrocytes and myelin sheaths as it is observed in multiple sclerosis. The proteins encoded ...
Source: Glia - November 14, 2018 Category: Neurology Authors: Peter G öttle, Moritz Förster, Joel Gruchot, David Kremer, Hans Peter Hartung, Hervé Perron, Patrick Küry Tags: RESEARCH ARTICLE Source Type: research