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Glia

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https://www.readbyqxmd.com/read/30208253/nbce1-mediates-the-regulation-of-the-nadh-nad-redox-state-in-cortical-astrocytes-by-neuronal-signals
#1
Susanne Köhler, Ulrike Winkler, Marit Sicker, Johannes Hirrlinger
Astrocytes are a glial cell type, which is indispensable for brain energy metabolism. Within cells, the NADH/NAD+ redox state is a crucial node in metabolism connecting catabolic pathways to oxidative phosphorylation and ATP production in mitochondria. To characterize the dynamics of the intracellular NADH/NAD+ redox state in cortical astrocytes Peredox, a genetically encoded sensor for the NADH/NAD+ redox state, was expressed in cultured cortical astrocytes as well as in cortical astrocytes in acutely isolated brain slices...
September 12, 2018: Glia
https://www.readbyqxmd.com/read/30208252/the-tam-receptor-tyro3-is-a-critical-regulator-of-myelin-thickness-in-the-central-nervous-system
#2
Farrah Blades, Andrea Aprico, Rainer Akkermann, Sarah Ellis, Michele D Binder, Trevor J Kilpatrick
Multiple sclerosis (MS) is an autoimmune, demyelinating disease of the central nervous system (CNS). Major deficits arise in MS patients due to an inability to repair damaged myelin sheaths following CNS insult, resulting in prolonged axonal exposure and neurodegeneration. The TAM receptors (Tyro3, Axl, and Mertk) have been implicated in MS susceptibility, demyelination and remyelination. Previously, we have shown that Tyro3 regulates developmental myelination and myelin thickness within the optic nerve and rostral region of the corpus callosum (CC) of adult mice...
September 12, 2018: Glia
https://www.readbyqxmd.com/read/30195261/how-to-reprogram-microglia-toward-beneficial-functions
#3
REVIEW
Marta Fumagalli, Marta Lombardi, Pierre Gressens, Claudia Verderio
Microglia, brain cells of nonneural origin, orchestrate the inflammatory response to diverse insults, including hypoxia/ischemia or maternal/fetal infection in the perinatal brain. Experimental studies have demonstrated the capacity of microglia to recognize pathogens or damaged cells activating a cytotoxic response that can exacerbate brain damage. However, microglia display an enormous plasticity in their responses to injury and may also promote resolution stages of inflammation and tissue regeneration. Despite the critical role of microglia in brain pathologies, the cellular mechanisms that govern the diverse phenotypes of microglia are just beginning to be defined...
September 8, 2018: Glia
https://www.readbyqxmd.com/read/30194875/nav1-5-in-astrocytes-plays-a-sex-specific-role-in-clinical-outcomes-in-a-mouse-model-of-multiple-sclerosis
#4
Laura W Pappalardo, Omar A Samad, Shujun Liu, Pamela J Zwinger, Joel A Black, Stephen G Waxman
Astrogliosis is a hallmark of neuroinflammatory disorders such as multiple sclerosis (MS). A detailed understanding of the underlying molecular mechanisms governing astrogliosis might facilitate the development of therapeutic targets. We investigated whether Nav1.5 expression in astrocytes plays a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We created a conditional knockout of Nav1.5 in astrocytes and determined whether this affects the clinical course of EAE, focal macrophage and T cell infiltration, and diffuse activation of astrocytes...
September 8, 2018: Glia
https://www.readbyqxmd.com/read/30194744/comparison-of-the-detrimental-features-of-microglia-and-infiltrated-macrophages-in-traumatic-brain-injury-a-study-using-a-hypnotic-bromovalerylurea
#5
Naoki Abe, Mohammed E Choudhury, Minori Watanabe, Shun Kawasaki, Tasuku Nishihara, Hajime Yano, Shirabe Matsumoto, Takehiro Kunieda, Yoshiaki Kumon, Toshihiro Yorozuya, Junya Tanaka
Microglia and blood-borne macrophages in injured or diseased brains are difficult to distinguish because they share many common characteristics. However, the identification of microglia-specific markers and the use of flow cytometry have recently made it easy to discriminate these types of cells. In this study, we analyzed the features of blood-borne macrophages, and activated and resting microglia in a rat traumatic brain injury (TBI) model. Oxidative injury was indicated in macrophages and neurons in TBI lesions by the presence of 8-hydroxy-2'-deoxyguanosine (8-OHdG)...
September 8, 2018: Glia
https://www.readbyqxmd.com/read/30152044/astrocytes-and-neurons-produce-distinct-types-of-polyglucosan-bodies-in-lafora-disease
#6
Elisabet Augé, Carme Pelegrí, Gemma Manich, Itsaso Cabezón, Joan J Guinovart, Jordi Duran, Jordi Vilaplana
Lafora disease (LD), the most devastating adolescence-onset epilepsy, is caused by mutations in the EPM2A or EPM2B genes, which encode the proteins laforin and malin, respectively. Loss of function of one of these proteins, which are involved in the regulation of glycogen synthesis, induces the accumulation of polyglucosan bodies (PGBs)-known as Lafora bodies (LBs) and associated with neurons-in the brain. Ageing and some neurodegenerative conditions lead to the appearance of another type of PGB called corpora amylacea, which are associated with astrocytes and contain neo-epitopes that can be recognized by natural antibodies...
August 26, 2018: Glia
https://www.readbyqxmd.com/read/30152028/sox17-transcription-factor-negatively-regulates-oligodendrocyte-precursor-cell-differentiation
#7
Melissa Fauveau, Baptiste Wilmet, Cyrille Deboux, Karelle Benardais, Corinne Bachelin, Ana C Temporão, Christophe Kerninon, Brahim Nait Oumesmar
Oligodendrocyte development is a critical process timely and spatially regulated to ensure proper myelination of the central nervous system. HMG-box transcription factors are key regulators of oligodendrocyte lineage progression. Among these factors, Sox17 was previously identified as a positive regulator of oligodendrocyte development. However, the role of Sox17 in oligodendroglial cell lineage progression and differentiation is still poorly understood. To define the functional role of Sox17, we generated new transgenic mouse models with inducible overexpression of Sox17, specifically in oligodendroglial cells...
August 26, 2018: Glia
https://www.readbyqxmd.com/read/30151916/fa%C3%A3-anas-cells-the-forgotten-cerebellar-glia-cell-type-immunocytochemistry-reveals-two-potassium-channel-related-polypeptides-kv2-2-and-calsenilin-kchip3-as-potential-marker-proteins
#8
Angelika Goertzen, Rüdiger W Veh
For long times astrocytes had been regarded as supporting cells, passively filling the spaces between neuronal cell bodies and their extensions. Now it is known that astrocytes are actively involved in a variety of important biological functions such as regulating cerebral blood flow, supporting neuronal metabolism, controlling the extracellular potassium concentration, and clearing neurotransmitters from the extracellular space. In line with this multitude of tasks astrocytes display conspicuous functional and regional heterogeneity...
August 26, 2018: Glia
https://www.readbyqxmd.com/read/30151840/enhanced-oligodendrocyte-maturation-and-myelination-in-a-mouse-model-of-timothy-syndrome
#9
Veronica T Cheli, Diara A Santiago González, Norma N Zamora, Tenzing N Lama, Vilma Spreuer, Randall L Rasmusson, Glenna C Bett, Georgia Panagiotakos, Pablo M Paez
To study the role of L-type voltage-gated Ca++ channels in oligodendrocyte development, we used a mouse model of Timothy syndrome (TS) in which a gain-of-function mutation in the α1 subunit of the L-type Ca++ channel Cav1.2 gives rise to an autism spectrum disorder (ASD). Oligodendrocyte progenitor cells (OPCs) isolated from the cortex of TS mice showed greater L-type Ca++ influx and displayed characteristics suggestive of advanced maturation compared to control OPCs, including a more complex morphology and higher levels of myelin protein expression...
August 26, 2018: Glia
https://www.readbyqxmd.com/read/30144323/directional-coupling-of-oligodendrocyte-connexin-47-and-astrocyte-connexin-43-gap-junctions
#10
Ilaria Fasciani, Paula Pluta, Daniel González-Nieto, Paloma Martínez-Montero, Jesús Molano, Carlos L Paíno, Oscar Millet, Luis C Barrio
Intercellular communication via gap junction channels between oligodendrocytes and between astrocytes as well as between these cell types is essential to maintain the integrity of myelin in the central nervous system. Oligodendrocyte gap junction connexin-47 (Cx47) is a key element in this crosstalk and indeed, mutations in human Cx47 cause severe myelin disorders. However, the permeation properties of channels of Cx47 alone and in heterotypic combination with astrocyte Cx43 remain unclear. We show here that Cx47 contains three extra residues at 5' amino-terminus that play a critical role in the channel pore structure and account for relative low ionic conductivity, cationic permselectivity and voltage-gating properties of oligodendrocyte-oligodendrocyte Cx47 channels...
August 25, 2018: Glia
https://www.readbyqxmd.com/read/30144321/microglia-heterogeneity-along-a-spatio-temporal-axis-more-questions-than-answers
#11
REVIEW
Aymeric Silvin, Florent Ginhoux
Microglia are resident macrophages of the central nervous system; they arise during early embryonic development and persist throughout adulthood. These unique cells provide developmental support, contribute to adult brain homeostasis and impart immune protection during infection. Dysregulated microglia are implicated in the pathophysiology of several neurological disorders, including Alzheimer disease, and as such, a better understanding of their regulation and function is required for rational therapeutic design...
August 25, 2018: Glia
https://www.readbyqxmd.com/read/30144320/increased-expression-of-colony-stimulating-factor-1-in-mouse-spinal-cord-with-experimental-autoimmune-encephalomyelitis-correlates-with-microglial-activation-and-neuronal-loss
#12
Svetlana Gushchina, Gareth Pryce, Ping K Yip, Dongsheng Wu, Patrick Pallier, Gavin Giovannoni, David Baker, Xuenong Bo
Microglia contribute to pathophysiology at all stages of multiple sclerosis. Colony-stimulating factor-1 (CSF1) is crucial for microglial proliferation and activation. In this study we measured the CSF1 levels and studied its cellular expression in the mouse spinal cords with experimental autoimmune encephalomyelitis (EAE) to explore the potential contribution of CSF1 in neuronal death. ELISA data showed that CSF1 levels were significantly higher in the spinal cords with acute and chronic EAE than those of normal and adjuvant-injected mice...
August 25, 2018: Glia
https://www.readbyqxmd.com/read/30144319/insights-into-the-release-mechanism-of-astrocytic-glutamate-evoking-in-neurons-nmda-receptor-mediated-slow-depolarizing-inward-currents
#13
Marta Gómez-Gonzalo, Tamara Zehnder, Linda Maria Requie, Paola Bezzi, Giorgio Carmignoto
The gliotransmitter glutamate in different brain regions modulates neuronal excitability and synaptic transmission through a variety of mechanisms. Among the hallmarks of astrocytic glutamate release are the slow depolarizing inward currents (SICs) in neurons mediated by N-methyl-d-aspartate receptor activation. Different stimuli that evoke Ca2+ elevations in astrocytes induce neuronal SICs suggesting a Ca2+ -dependent exocytotic glutamate release mechanism of SIC generation. To gain new insights into this mechanism, we investigated the relationship between astrocytic Ca2+ elevations and neuronal SICs in mouse hippocampal slice preparations...
August 25, 2018: Glia
https://www.readbyqxmd.com/read/30098078/metallothionein-i-ii-expression-associates-with-the-astrocyte-dna-damage-response-and-not-alzheimer-type-pathology-in-the-aging-brain
#14
Rachel Waller, Mark Murphy, Claire J Garwood, Luke Jennings, Paul R Heath, Annabelle Chambers, Fiona E Matthews, Carol Brayne, Paul G Ince, Stephen B Wharton, Julie E Simpson
Oxidative stress and oxidative DNA damage are early features of mild cognitive impairment and Alzheimer's disease (AD), occurring before the formation of classical AD neuropathology, and resulting from an imbalance between pro- and anti-oxidants. Astrocytes play a major neuroprotective role, producing high levels of anti-oxidants including metallothionein-I and -II (MT-I/II). In the present study we characterized the immunoreactive profile of MT-I/II in the temporal cortex of the Cognitive Function and Ageing Study (CFAS) aging population-representative neuropathology cohort, and examined H2 O2 -modulation of MT transcription by human astrocytes...
August 10, 2018: Glia
https://www.readbyqxmd.com/read/30051922/microglia-have-a-more-extensive-and-divergent-response-to-interferon-%C3%AE-compared-with-astrocytes
#15
Wen Li, Barney Viengkhou, Gareth Denyer, Phillip K West, Iain L Campbell, Markus J Hofer
Type I interferons (IFN-I) are crucial for effective antimicrobial defense in the central nervous system (CNS) but also can cause severe neurological disease (termed cerebral interferonopathy) as exemplified by Aicardi-Goutières Syndrome. In the CNS, microglia and astrocytes have essential roles in host responses to infection and injury, with both cell types responding to IFN-I. While the IFN-I signaling pathways are the same in astrocytes and microglia, the extent to which the IFN-I responses of these cells differ, if at all, is unknown...
July 27, 2018: Glia
https://www.readbyqxmd.com/read/30051920/nogo-a-inhibits-vascular-regeneration-in-ischemic-retinopathy
#16
Sandrine Joly, Agnieszka Dejda, Léa Rodriguez, Przemyslaw Sapieha, Vincent Pernet
Nogo-A is a potent glial-derived inhibitor of axon growth in the injured CNS and acts as a negative regulator of developmental angiogenesis by inhibiting vascular endothelial cell migration. However, its function in pathological angiogenesis has never been studied after ischemic injury in the CNS. Using the mouse model of oxygen-induced retinopathy (OIR) which yields defined zones of retinal ischemia, our goal was to investigate the role of Nogo-A in vascular regeneration. We demonstrate a marked upregulation of the Nogo-A receptor sphingosine 1-phosphate receptor 2 in blood vessels following OIR, while Nogo-A is abundantly expressed in surrounding glial cells...
July 27, 2018: Glia
https://www.readbyqxmd.com/read/30043530/astroglia-contribute-to-the-pathogenesis-of-spinocerebellar-ataxia-type-1-sca1-in-a-biphasic-stage-of-disease-specific-manner
#17
Joo Hyun Kim, Abigail Lukowicz, Wenhui Qu, Andrea Johnson, Marija Cvetanovic
Spinocerebellar ataxia type 1 (SCA1) is a fatal, dominantly inherited neurodegenerative disease caused by the expansion of CAG repeats in the Ataxin-1 (ATXN1) gene. SCA1 is characterized by balance and coordination deficits due to the predominant loss of Purkinje neurons in the cerebellum. We previously demonstrated that cerebellar astrogliosis beings during the early stages of SCA1, prior to onset of motor deficits and loss of Purkinje neurons. We communicate here that cerebellar astrogliosis contributes to SCA1 pathogenesis in a biphasic, stage of disease dependent manner...
July 25, 2018: Glia
https://www.readbyqxmd.com/read/30043519/neuronal-activity-induces-glutathione-metabolism-gene-expression-in-astrocytes
#18
James C McGann, Gail Mandel
The idea that astrocytes provide support for neurons has a long history, but whether neurons play an instructive role in these processes is poorly understood. To address this question, we co-culture astrocytes with genetically labeled neurons, permitting their separation by flow cytometry, and test whether the presence of neurons influences the astrocyte transcriptome. We find that numerous pathways are regulated in the co-cultured astrocytes, in a time-dependent matter coincident with synaptic maturation. In particular, the induction of glutathione metabolic genes is prominent, resulting in increased glutathione production...
July 25, 2018: Glia
https://www.readbyqxmd.com/read/30043461/selective-role-of-na-h-exchanger-in-cx3cr1-microglial-activation-white-matter-demyelination-and-post-stroke-function-recovery
#19
Shanshan Song, Shaoxia Wang, Victoria M Pigott, Tong Jiang, Lesley M Foley, Abhishek Mishra, Rachana Nayak, Wen Zhu, Gulnaz Begum, Yejie Shi, Karen E Carney, T Kevin Hitchens, Gary E Shull, Dandan Sun
Na+ /H+ exchanger (NHE1) activation is required for multiple microglial functions. We investigated effects of selective deletion of microglial Nhe1 in Cx3cr1-CreER ;Nhe1f/f mice on neuroinflammation and tissue repair after ischemic stroke. Infarct volume was similar in corn oil or tamoxifen (Tam)-treated mice at 48 hr and 14 days post-stroke. However, the Tam-treated mice showed significantly higher survival rate and faster neurological function recovery during day 1-14 post-stroke. Deletion of microglial Nhe1 prevented the elevation of CD11b+ /CD45low-med microglia in the ischemic hemisphere at day 3 post-stroke, but stimulated expression of Ym1, CD68, TGF-β, IL-10, decreased expression of CD86 and IL-1β, and reduced GFAP+ reactive astrocytes...
July 25, 2018: Glia
https://www.readbyqxmd.com/read/30043400/the-voltage-gated-potassium-channel-kv1-3-is-required-for-microglial-pro-inflammatory-activation-in-vivo
#20
Jacopo Di Lucente, Hai M Nguyen, Heike Wulff, Lee-Way Jin, Izumi Maezawa
Microglia show a rich repertoire of activation patterns regulated by a complex ensemble of surface ion channels, receptors, and transporters. We and others have investigated whether microglia vary their K+ channel expression as a means to achieve functional diversity. However, most of the prior studies were conducted using in vitro models such as BV2 cells, primary microglia, or brain slices in culture, which may not accurately reflect microglia physiology in adult individuals. Here we employed an in vivo mouse model of selective innate immune activation by intracerebroventricular injection of lipopolysaccharides (ICV-LPS) to determine the role of the voltage-gated Kv1...
July 25, 2018: Glia
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