Bioenergetic regulation of microglia
Abstract
Microglia have diverse actions, ranging from synapse pruning in development to cytotoxic effects in disease. Brain energy metabolism and substrate availability vary under normal and disease states, but how these variations influence microglial function is relatively unknown. Microglia, like most other cell types, express the full complement of gene products required for both glycolytic and oxidative metabolism. Evidence suggests that microglia increase aerobic glycolysis and decrease respiration when activated by various stimuli. Mitochondrial function, glucose availability, and glycolytic rate influence pro‐inf...
Source: Glia - December 8, 2017 Category: Neurology Authors: Soumitra Ghosh, Erika Castillo, Elma S. Frias, Raymond A. Swanson Tags: REVIEW Source Type: research
Bioenergetic regulation of microglia
Glia, EarlyView. (Source: Glia)
Source: Glia - December 8, 2017 Category: Neurology Source Type: research
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Glia, Ahead of Print. (Source: Glia)
Source: Glia - December 8, 2017 Category: Neurology Source Type: research
Region ‐specific deletions of the glutamate transporter GLT1 differentially affect seizure activity and neurodegeneration in mice
In this study, we generated region‐specific GLT1 knockout mice by crossing floxed‐GLT1 mice with mice that express the Cre recombinase in a particular domain of the ventricular zone. Selective deletion of GLT1 in the diencephalon, brainstem and spinal cord is sufficient to reproduce the phenotypes (excess mortality, decreased body weight, and lethal spontaneous seizure) of the global GLT1 null mice. By contrast, dorsal forebrain‐specific GLT1 knockout mice showed nonlethal complex seizures including myoclonic jerks, hyperkinetic running, spasm and clonic convulsion via the activation of NMDA receptors during a limite...
Source: Glia - December 7, 2017 Category: Neurology Authors: Junya Sugimoto, Moeko Tanaka, Kaori Sugiyama, Yukiko Ito, Hidenori Aizawa, Miho Soma, Tomoko Shimizu, Akira Mitani, Kohichi Tanaka Tags: RESEARCH ARTICLE Source Type: research
Myelination and mTOR
Abstract
Myelinating cells surround axons to accelerate the propagation of action potentials, to support axonal health, and to refine neural circuits. Myelination is metabolically demanding and, consistent with this notion, mTORC1—a signaling hub coordinating cell metabolism—has been implicated as a key signal for myelination. Here, we will discuss metabolic aspects of myelination, illustrate the main metabolic processes regulated by mTORC1, and review advances on the role of mTORC1 in myelination of the central nervous system and the peripheral nervous system. Recent progress has revealed a complex role of mTORC1 in m...
Source: Glia - December 6, 2017 Category: Neurology Authors: Gianluca Figlia, Daniel Gerber, Ueli Suter Tags: REVIEW ARTICLE Source Type: research
Functional antagonism of sphingosine ‐1‐phosphate receptor 1 prevents cuprizone‐induced demyelination
Abstract
Recent evidence suggests that the oral drug Fingolimod (FTY720) for relapsing‐remitting multiple sclerosis (MS) may act directly on the central nervous system (CNS) and modulate disease pathogenesis and progression in experimental models of MS. However, the specific subtype of sphingosine‐1‐phosphate (S1P) receptors that mediates the effect of FTY720 on the CNS cells has not been fully elucidated. Here, we report that S1P receptor 1 (S1PR1) is elevated in reactive astrocytes in an autoimmunity independent mouse model of MS and that selective S1PR1 modulation is sufficient to ameliorate the loss of oligodendr...
Source: Glia - November 29, 2017 Category: Neurology Authors: SunJa Kim, Jacek Bielawski, Hyunmin Yang, Yu Kong, Beiyan Zhou, Jianrong Li Tags: RESEARCH ARTICLE Source Type: research
Sox2 regulates astrocytic and vascular development in the retina
Abstract
Sox2 is a transcriptional regulator that is highly expressed in retinal astrocytes, yet its function in these cells has not previously been examined. To understand its role, we conditionally deleted Sox2 from the population of astrocytes and examined the consequences on retinal development. We found that Sox2 deletion does not alter the migration of astrocytes, but it impairs their maturation, evidenced by the delayed upregulation of glial fibrillary acidic protein (GFAP) across the retina. The centro‐peripheral gradient of angiogenesis is also delayed in Sox2‐CKO retinas. In the mature retina, we observed las...
Source: Glia - November 27, 2017 Category: Neurology Authors: Amanda G. Kautzman, Patrick W. Keeley, Michael M. Nahmou, Gabriel Luna, Steven K. Fisher, Benjamin E. Reese Tags: RESEARCH ARTICLE Source Type: research
Phagocytic clearance of presynaptic dystrophies by reactive astrocytes in Alzheimer's disease
In this study, using immunohistochemical techniques and light and electron microscopy, we report that plaque‐associated reactive astrocytes enwrap, engulf and may digest presynaptic dystrophies in the hippocampus of amyloid precursor protein/presenilin‐1 (APP/PS1) mice. Microglia, the brain phagocytic population, was apparently not engaged in this clearance. Phagocytic reactive astrocytes were present in 35% and 67% of amyloid plaques at 6 and 12 months of age, respectively. The proportion of engulfed dystrophic neurites was low, around 7% of total dystrophies around plaques at both ages. This fact, along with the acc...
Source: Glia - November 27, 2017 Category: Neurology Authors: Angela Gomez ‐Arboledas, Jose C. Davila, Elisabeth Sanchez‐Mejias, Victoria Navarro, Cristina Nuñez‐Diaz, Raquel Sanchez‐Varo, Maria Virtudes Sanchez‐Mico, Laura Trujillo‐Estrada, Juan Jose Fernandez‐Valenzuela, Marisa Vizuete, Joan X. Come Tags: RESEARCH ARTICLE Source Type: research
Glial hypothalamic inhibition of GLUT2 expression alters satiety, impacting eating behavior
This study aimed to clarify the role of GLUT2 expression in tanycytes in feeding behavior using 3V injections of an adenovirus encoding a shRNA against GLUT2 and the reporter EGFP (Ad‐shGLUT2). Efficient in vivo GLUT2 knockdown in rat hypothalamic tissue was demonstrated by qPCR and Western blot analyses. Specificity of cell transduction in the hypothalamus and brainstem was evaluated by EGFP‐fluorescence and immunohistochemistry, which showed EGFP expression specifically in ependymal cells, including tanycytes. The altered mRNA levels of both orexigenic and anorexigenic neuropeptides suggested a loss of response to in...
Source: Glia - November 27, 2017 Category: Neurology Authors: Mar ía J. Barahona, Paula Llanos, Antonia Recabal, Kathleen Escobar‐Acuña, Roberto Elizondo‐Vega, Magdiel Salgado, Patricio Ordenes, Elena Uribe, Fernando J. Sepúlveda, Ricardo C. Araneda, María A. García‐Robles Tags: RESEARCH ARTICLE Source Type: research
Regional oligodendrocytopathy and astrocytopathy precede myelin loss and blood –brain barrier disruption in a murine model of osmotic demyelination syndrome
In conclusion, this murine model of ODS reproduces the CNS demyelination observed in human pathology and indicates ambiguous causes that is regional vulnerability of oligodendrocytes and astrocytes, while it discards BBB disruption as a primary cause of demyelination. This study also raises new queries about the glial heterogeneity in susceptible brain regions as well as about the early microglial activation associated with ODS.
Main Points
Rapid correction of chronic severe hyponatremia in mouse leads to functional impairments mimicking those found in ODS patients
In this model, necroptosis drives glial cell death in sp...
Source: Glia - November 23, 2017 Category: Neurology Authors: Joanna Bouchat, Bruno Couturier, Catherine Marneffe, Fabrice Gankam ‐Kengne, Benoît Balau, Kathleen De Swert, Jean‐Pierre Brion, Luc Poncelet, Jacques Gilloteaux, Charles Nicaise Tags: RESEARCH ARTICLE Source Type: research
The function of contactin ‐2/TAG‐1 in oligodendrocytes in health and demyelinating pathology.
Abstract
The oligodendrocyte maturation process and the transition from the pre‐myelinating to the myelinating state are extremely important during development and in pathology. In the present study, we have investigated the role of the cell adhesion molecule CNTN2/TAG‐1 on oligodendrocyte proliferation, differentiation, myelination, and function during development and under pathological conditions. With the combination of in vivo, in vitro, ultrastructural, and electrophysiological methods, we have mapped the expression of CNTN2 protein in the oligodendrocyte lineage during the different stages of myelination and its ...
Source: Glia - November 22, 2017 Category: Neurology Authors: Lida Zoupi, Maria Savvaki, Katerina Kalemaki, Ilias Kalafatakis, Kyriaki Sidiropoulou, Domna Karagogeos Tags: RESEARCH ARTICLE Source Type: research
The function of contactin ‐2/TAG‐1 in oligodendrocytes in health and demyelinating pathology
Abstract
The oligodendrocyte maturation process and the transition from the pre‐myelinating to the myelinating state are extremely important during development and in pathology. In the present study, we have investigated the role of the cell adhesion molecule CNTN2/TAG‐1 on oligodendrocyte proliferation, differentiation, myelination, and function during development and under pathological conditions. With the combination of in vivo, in vitro, ultrastructural, and electrophysiological methods, we have mapped the expression of CNTN2 protein in the oligodendrocyte lineage during the different stages of myelination and its ...
Source: Glia - November 22, 2017 Category: Neurology Authors: Lida Zoupi, Maria Savvaki, Katerina Kalemaki, Ilias Kalafatakis, Kyriaki Sidiropoulou, Domna Karagogeos Tags: RESEARCH ARTICLE Source Type: research
Neuregulin ‐1 promotes remyelination and fosters a pro‐regenerative inflammatory response in focal demyelinating lesions of the spinal cord
In conclusion, Nrg‐1 promotes a pro‐regenerative microenvironment that fosters oligodendrocyte replacement and enhances remyelination process in demyelinating lesions of the central nervous system. (Source: Glia)
Source: Glia - November 17, 2017 Category: Neurology Authors: Hardeep Kataria, Arsalan Alizadeh, Ghazaleh M. Shahriary, Shekoofeh Saboktakin Rizi, Ryan Henrie, Kallivalappil T. Santhosh, James A. Thliveris, Soheila Karimi ‐Abdolrezaee Tags: RESEARCH ARTICLE Source Type: research
Issue Information ‐ Table of Contents
(Source: Glia)
Source: Glia - November 17, 2017 Category: Neurology Tags: ISSUE INFORMATION ‐ TABLE OF CONTENTS Source Type: research
A critical role of TRPM2 channel in A β42‐induced microglial activation and generation of tumor necrosis factor‐α
Abstract
Amyloid β (Aβ)‐induced neuroinflammation plays an important part in Alzheimer's disease (AD). Emerging evidence supports a role for the transient receptor potential melastatin‐related 2 (TRPM2) channel in Aβ‐induced neuroinflammation, but how Aβ induces TRPM2 channel activation and this relates to neuroinflammation remained poorly understood. We investigated the mechanisms by which Aβ42 activates the TRPM2 channel in microglial cells and the relationships to microglial activation and generation of tumor necrosis factor‐α (TNF‐α), a key cytokine implicated in AD. Exposure to 10–300 nM Aβ42 indu...
Source: Glia - November 16, 2017 Category: Neurology Authors: Sharifah Alawieyah Syed Mortadza, Joan A Sim, Veronika E Neubrand, Lin ‐Hua Jiang Tags: RESEARCH ARTICLE Source Type: research
