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https://www.readbyqxmd.com/read/28636132/trpc1-and-trpc3-dependent-ca-2-signaling-in-mouse-cortical-astrocytes-affects-injury-evoked-astrogliosis-in-vivo
#1
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...
June 21, 2017: Glia
https://www.readbyqxmd.com/read/28631858/sensory-response-in-host-and-engrafted-astrocytes-of-adult-brain-in-vivo
#2
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/28618115/iron-sulfur-glutaredoxin-2-protects-oligodendrocytes-against-damage-induced-by-nitric-oxide-release-from-activated-microglia
#3
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...
June 15, 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
#4
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...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28618073/drug-discovery-for-remyelination-and-treatment-of-ms
#5
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/28617998/schwann-cell-specific-deletion-of-the-endosomal-pi-3-kinase-vps34-leads-to-delayed-radial-sorting-of-axons-arrested-myelination-and-abnormal-erbb2-erbb3-tyrosine-kinase-signaling
#6
Anne M Logan, Anna E Mammel, Danielle C Robinson, Andrea L Chin, Alec F Condon, Fred L Robinson
The PI 3-kinase Vps34 (Pik3c3) synthesizes phosphatidylinositol 3-phosphate (PI3P), a lipid critical for both endosomal membrane traffic and macroautophagy. Human genetics have implicated PI3P dysregulation, and endosomal trafficking in general, as a recurring cause of demyelinating Charcot-Marie-Tooth (CMT) peripheral neuropathy. Here, we investigated the role of Vps34, and PI3P, in mouse Schwann cells by selectively deleting Vps34 in this cell type. Vps34-Schwann cell knockout (Vps34(SCKO) ) mice show severe hypomyelination in peripheral nerves...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28617991/interferon-%C3%AE-regulates-the-production-of-il-10-by-toll-like-receptor-activated-microglia
#7
Diogo Lobo-Silva, Guilhermina M Carriche, A Gil Castro, Susana Roque, Margarida Saraiva
Pattern recognition receptors, such as toll-like receptors (TLRs), perceive tissue alterations and initiate local innate immune responses. Microglia, the resident macrophages of the brain, encode TLRs which primary role is to protect the tissue integrity. However, deregulated activation of TLRs in microglia may lead to chronic neurodegeneration. This double role of microglial responses is often reported in immune-driven neurologic diseases, as in multiple sclerosis (MS). Consequently, strategies to manipulate microglia inflammatory responses may help to ameliorate disease progression...
June 15, 2017: Glia
https://www.readbyqxmd.com/read/28608978/sexual-dimorphism-in-the-inflammatory-response-to-traumatic-brain-injury
#8
Sonia Villapol, David J Loane, Mark P Burns
The activation of resident microglial cells, alongside the infiltration of peripheral macrophages, are key neuroinflammatory responses to traumatic brain injury (TBI) that are directly associated with neuronal death. Sexual disparities in response to TBI have been previously reported; however it is unclear whether a sex difference exists in neuroinflammatory progression after TBI. We exposed male and female mice to moderate-to-severe controlled cortical impact injury and studied glial cell activation in the acute and chronic stages of TBI using immunofluorescence and in situ hybridization analysis...
June 13, 2017: Glia
https://www.readbyqxmd.com/read/28581152/neurosteroid-dehydroepiandrosterone-enhances-activity-and-trafficking-of-astrocytic-glt-1-via-%C3%AF-1-receptor-mediated-pkc-activation-in-the-hippocampal-dentate-gyrus-of-rats
#9
Tingting Chen, Motoki Tanaka, Ya Wang, Sha Sha, Kishio Furuya, Ling Chen, Masahiro Sokabe
Neurosteroid dehydroepiandrosterone (DHEA) has been reported to exert a potent neuroprotective effect against glutamate-induced excitotoxicity. However, the underlying mechanism remains to be elucidated. One of the possible mechanisms may be an involvement of astrocytic glutamate transporter subtype-1 (GLT-1) that can quickly clear spilled glutamate at the synapse to prevent excitotoxicity. To examine the effect of DHEA on GLT-1 activity, we measured synaptically induced glial depolarization (SIGD) in the dentate gyrus (DG) of adult rats by applying an optical recording technique to the hippocampal slices stained with voltage-sensitive dye RH155...
June 5, 2017: Glia
https://www.readbyqxmd.com/read/28581123/astrocyte-derived-lipocalin-2-mediates-hippocampal-damage-and-cognitive-deficits-in-experimental-models-of-vascular-dementia
#10
Jae-Hong Kim, Pan-Woo Ko, Ho-Won Lee, Ji-Young Jeong, Maan-Gee Lee, Jong-Heon Kim, Won-Ha Lee, Ri Yu, Won-Jong Oh, Kyoungho Suk
Lipocalin-2 (LCN2) has diverse functions in multiple pathophysiological conditions; however, its pathogenic role in vascular dementia (VaD) is unknown. Here, we investigated the role of LCN2 in VaD using rodent models of global cerebral ischemia and hypoperfusion with cognitive impairment and neuroinflammation. Mice subjected to transient bilateral common carotid artery occlusion (tBCCAo) for 50 min showed neuronal death and gliosis in the hippocampus at 7 days post-tBCCAo. LCN2 expression was observed predominantly in the hippocampal astrocytes, whereas its receptor was mainly detected in neurons, microglia, and astrocytes...
June 5, 2017: Glia
https://www.readbyqxmd.com/read/28569048/astrocyte-mediated-synapse-remodeling-in-the-pathological-brain
#11
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/28568966/neuroinflammation-as-modifier-of-genetically-caused-neurological-disorders-of-the-central-nervous-system-understanding-pathogenesis-and-chances-for-treatment
#12
REVIEW
Janos Groh, Rudolf Martini
Genetically caused neurological disorders of the central nervous system (CNS) are usually orphan diseases with poor or even fatal clinical outcome and few or no treatments that will improve longevity or at least quality of life. Neuroinflammation is common to many of these disorders, despite the fact that a plethora of distinct mutations and molecular changes underlie the disorders. In this article, data from corresponding animal models are analyzed to define the roles of innate and adaptive inflammation as modifiers and amplifiers of disease...
June 1, 2017: Glia
https://www.readbyqxmd.com/read/28519900/type-i-interferon-pathway-in-cns-homeostasis-and-neurological-disorders
#13
REVIEW
Thomas Blank, Marco Prinz
Type I interferons (IFNs), IFN-α and IFN-β, represent the major effector cytokines of the host immune response against viruses and other intracellular pathogens. These cytokines are produced via activation of numerous pattern recognition receptors, including the Toll-like receptor signaling network, retinoic acid-inducible gene-1 (RIG-1), melanoma differentiation-associated protein-5 (MDA-5) and interferon gamma-inducible protein-16 (IFI-16). Whilst the contribution of type I IFNs to peripheral immunity is well documented, they can also be produced by almost every cell in the central nervous system (CNS)...
May 18, 2017: Glia
https://www.readbyqxmd.com/read/28471051/a-presumed-antagonistic-lps-identifies-distinct-functional-organization-of-tlr4-in-mouse-microglia
#14
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
#15
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
#16
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/28417486/age-specific-function-of-%C3%AE-5%C3%AE-1-integrin-in-microglial-migration-during-early-colonization-of-the-developing-mouse-cortex
#17
Sophie Marie-Thérèse Smolders, Nina Swinnen, Sofie Kessels, Kaline Arnauts, Silke Smolders, Barbara Le Bras, Jean-Michel Rigo, Pascal Legendre, Bert Brône
Microglia, the immune cells of the central nervous system, take part in brain development and homeostasis. They derive from primitive myeloid progenitors that originate in the yolk sac and colonize the brain mainly through intensive migration. During development, microglial migration speed declines which suggests that their interaction with the microenvironment changes. However, the matrix-cell interactions allowing dispersion within the parenchyma are unknown. Therefore, we aimed to better characterize the migration behavior and to assess the role of matrix-integrin interactions during microglial migration in the embryonic brain ex vivo...
April 18, 2017: Glia
https://www.readbyqxmd.com/read/28398652/brucella-abortus-activated-microglia-induce-neuronal-death-through-primary-phagocytosis
#18
Ana M Rodríguez, M Victoria Delpino, M Cruz Miraglia, Miriam M Costa Franco, Paula Barrionuevo, Vida A Dennis, Sergio C Oliveira, Guillermo H Giambartolomei
Inflammation has long been implicated as a contributor to pathogenesis in neurobrucellosis. Many of the associated neurocognitive symptoms of neurobrucellosis may be the result of neuronal dysfunction resulting from the inflammatory response induced by Brucella abortus infection in the central nervous system. In this manuscript, we describe an immune mechanism for inflammatory activation of microglia that leads to neuronal death upon B. abortus infection. B. abortus was unable to infect or harm primary cultures of mouse neurons...
April 11, 2017: Glia
https://www.readbyqxmd.com/read/28375547/demyelination-induced-by-oxidative-stress-is-regulated-by-sphingosine-1-phosphate-receptors
#19
Sinead A O'Sullivan, Maria Velasco-Estevez, Kumlesh K Dev
Oxidative stress is a pathological condition defined as an imbalance between production and removal of reactive oxygen species. This process causes structural cell damage, disrupts DNA repair and induces mitochondrial dysfunction. Many in vitro studies have used direct bolus application of H2 O2 to investigate the role of oxidative stress in cell culture. In this study, using mouse organotypic cerebellar slice cultures, the effects of H2 O2 -induced oxidative stress on myelination state were examined, using bolus concentrations of H2 O2 (0...
April 4, 2017: Glia
https://www.readbyqxmd.com/read/28370559/transcription-factor-sox10-regulates-oligodendroglial-sox9-levels-via-micrornas
#20
Simone Reiprich, Martina Cantone, Matthias Weider, Tina Baroti, Jan Wittstatt, Christian Schmitt, Melanie Küspert, Julio Vera, Michael Wegner
During development of myelin-forming oligodendrocytes in the central nervous system the two closely related transcription factors Sox9 and Sox10 play essential roles that are partly shared and partly unique. Whereas Sox9 primarily functions during oligodendroglial specification, Sox10 is uniquely required to induce terminal differentiation and myelination. During this process, Sox10 protein levels rise substantially. As this coincides with a reciprocal decrease in Sox9, we postulated that Sox10 influences Sox9 amounts in differentiating oligodendrocytes...
April 3, 2017: Glia
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