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https://www.readbyqxmd.com/read/29330881/cocaine-and-hiv-1-tat-disrupt-cholesterol-homeostasis-in-astrocytes-implications-for-hiv-associated-neurocognitive-disorders-in-cocaine-user-patients
#1
Bianca Cotto, Kalimuthusamy Natarajaseenivasan, Kimberly Ferrero, Leroy Wesley, Matthew Sayre, Dianne Langford
Cholesterol synthesis and clearance by astrocytes are tightly regulated to maintain constant levels within the brain. In this context, liver X receptors (LXRs) are the master regulators of cholesterol homeostasis in the central nervous system (CNS). Increasing levels of cholesterol in astrocytes trigger LXR activation leading to the transcription of target genes involved in cholesterol trafficking and efflux, including apolipoprotein E, cytochrome P450 enzymes, sterol regulatory binding protein, and several ATP-binding cassette transporter proteins...
January 13, 2018: Glia
https://www.readbyqxmd.com/read/29330870/cell-therapy-for-spinal-cord-injury-with-olfactory-ensheathing-glia-cells-oecs
#2
REVIEW
Rosa M Gómez, Magdy Y Sánchez, Maria Portela-Lomba, Kemel Ghotme, George E Barreto, Javier Sierra, M Teresa Moreno-Flores
The prospects of achieving regeneration in the central nervous system (CNS) have changed, as most recent findings indicate that several species, including humans, can produce neurons in adulthood. Studies targeting this property may be considered as potential therapeutic strategies to respond to injury or the effects of demyelinating diseases in the CNS. While CNS trauma may interrupt the axonal tracts that connect neurons with their targets, some neurons remain alive, as seen in optic nerve and spinal cord (SC) injuries (SCIs)...
January 13, 2018: Glia
https://www.readbyqxmd.com/read/29315804/white-matter-tauopathy-transient-functional-loss-and-novel-myelin-remodeling
#3
Joshua Jackson, Gabby Bianco, Angelo O Rosa, Katrina Cowan, Peter Bond, Oleg Anichtchik, Robert Fern
Early white matter (WM) changes are common in dementia and may contribute to functional decline. We here examine this phenomenon in an induced dementia model for the first time. We report a novel and selective form of myelin injury as the first manifestation of tauopathy in the adult central nervous system. Myelin pathology rapidly followed the induction of a P301 tau mutation associated with fronto-temporal dementia in humans (rTG4510 line). Damage involved focal disruption of the ad-axonal myelin lamella and internal oligodendrocyte tongue process, followed by myelin remodeling with features of re-myelination that included myelin thinning and internodal shortening...
January 8, 2018: Glia
https://www.readbyqxmd.com/read/29288597/fractionation-enhances-acute-oligodendrocyte-progenitor-cell-radiation-sensitivity-and-leads-to-long-term-depletion
#4
Sage Begolly, John A Olschowka, Tanzy Love, Jacqueline P Williams, M Kerry O'Banion
Ionizing radiation (IR) is commonly used to treat central nervous system (CNS) cancers and metastases. While IR promotes remission, frequent side effects including impaired cognition and white matter loss occur following treatment. Fractionation is used to minimize these CNS late side effects, as it reduces IR effects in differentiated normal tissue, but not rapidly proliferating normal or tumor tissue. However, side effects occur even with the use of fractionated paradigms. Oligodendrocyte progenitor cells (OPCs) are a proliferative population within the CNS affected by radiation...
December 30, 2017: Glia
https://www.readbyqxmd.com/read/29288586/promoij-a-new-tool-for-automatic-three-dimensional-analysis-of-microglial-process-motility
#5
Iñaki Paris, Julie C Savage, Laura Escobar, Oihane Abiega, Steven Gagnon, Chin-Wai Hui, Marie-Ève Tremblay, Amanda Sierra, Jorge Valero
Microglia, the immune cells of the central nervous system, continuously survey the brain to detect alterations and maintain tissue homeostasis. The motility of microglial processes is indicative of their surveying capacity in normal and pathological conditions. The gold standard technique to study motility involves the use of two-photon microscopy to obtain time-lapse images from brain slices or the cortex of living animals. This technique generates four dimensionally-coded images which are analyzed manually using time-consuming, non-standardized protocols...
December 30, 2017: Glia
https://www.readbyqxmd.com/read/29285798/affected-astrocytes-in-the-spinal-cord-of-the-leukodystrophy-vanishing-white-matter
#6
Prisca S Leferink, Nicole Breeuwsma, Marianna Bugiani, Marjo S van der Knaap, Vivi M Heine
Leukodystrophies are often devastating diseases, presented with progressive clinical signs as spasticity, ataxia and cognitive decline, and lack proper treatment options. New therapy strategies for leukodystrophies mostly focus on oligodendrocyte replacement to rescue lack of myelin in the brain, even though disease pathology also often involves other glial cells and the spinal cord. In this study we investigated spinal cord pathology in a mouse model for Vanishing White Matter disease (VWM) and show that astrocytes in the white matter are severely affected...
December 29, 2017: Glia
https://www.readbyqxmd.com/read/29285794/glial-lipid-droplets-and-neurodegeneration-in-a-drosophila-model-of-complex-i-deficiency
#7
Marie-Jeanne Cabirol-Pol, Bilal Khalil, Thomas Rival, Catherine Faivre-Sarrailh, Marie Thérèse Besson
Mitochondrial defects associated with respiratory chain complex I deficiency lead to heterogeneous fatal syndromes. While the role of NDUFS8, an essential subunit of the core assembly of the complex I, is established in mitochondrial diseases, the mechanisms underlying neuropathology are poorly understood. We developed a Drosophila model of NDUFS8 deficiency by knocking down the expression of its fly homologue in neurons or in glial cells. Downregulating ND23 in neurons resulted in shortened lifespan, and decreased locomotion...
December 29, 2017: Glia
https://www.readbyqxmd.com/read/29282769/glial-m6b-stabilizes-the-axonal-membrane-at-peripheral-nodes-of-ranvier
#8
Marie L Bang, Anya Vainshtein, Hyun-Jeong Yang, Yael Eshed-Eisenbach, Jerome Devaux, Hauke B Werner, Elior Peles
Glycoprotein M6B and the closely related proteolipid protein regulate oligodendrocyte myelination in the central nervous system, but their role in the peripheral nervous system is less clear. Here we report that M6B is located at nodes of Ranvier in peripheral nerves where it stabilizes the nodal axolemma. We show that M6B is co-localized and associates with gliomedin at Schwann cell microvilli that are attached to the nodes. Developmental analysis of sciatic nerves, as well as of myelinating Schwann cells/dorsal root ganglion neurons cultures, revealed that M6B is already present at heminodes, which are considered the precursors of mature nodes of Ranvier...
December 28, 2017: Glia
https://www.readbyqxmd.com/read/29274121/brain-metabolic-sensing-and-metabolic-signaling-at-the-level-of-an-astrocyte
#9
Nephtali Marina, Egor Turovsky, Isabel N Christie, Patrick S Hosford, Anna Hadjihambi, Alla Korsak, Richard Ang, Svetlana Mastitskaya, Shahriar Sheikhbahaei, Shefeeq M Theparambil, Alexander V Gourine
Astrocytes support neuronal function by providing essential structural and nutritional support, neurotransmitter trafficking and recycling and may also contribute to brain information processing. In this article we review published results and report new data suggesting that astrocytes function as versatile metabolic sensors of central nervous system (CNS) milieu and play an important role in the maintenance of brain metabolic homeostasis. We discuss anatomical and functional features of astrocytes that allow them to detect and respond to changes in the brain parenchymal levels of metabolic substrates (oxygen and glucose), and metabolic waste products (carbon dioxide)...
December 23, 2017: Glia
https://www.readbyqxmd.com/read/29274095/alterations-in-ca1-hippocampal-synapses-in-a-mouse-model-of-fragile-x-syndrome
#10
Safdar Jawaid, Grahame J Kidd, Jing Wang, Carrie Swetlik, Ranjan Dutta, Bruce D Trapp
Fragile X Syndrome (FXS) is the major cause of inherited mental retardation and the leading genetic cause of Autism spectrum disorders. FXS is caused by mutations in the Fragile X Mental Retardation 1 (Fmr1) gene, which results in transcriptional silencing of Fragile X Mental Retardation Protein (FMRP). To elucidate cellular mechanisms involved in the pathogenesis of FXS, we compared dendritic spines in the hippocampal CA1 region of adult wild-type (WT) and Fmr1 knockout (Fmr1-KO) mice. Using diolistic labeling, confocal microscopy, and three-dimensional electron microscopy, we show a significant increase in the diameter of secondary dendrites, an increase in dendritic spine density, and a decrease in mature dendritic spines in adult Fmr1-KO mice...
December 23, 2017: Glia
https://www.readbyqxmd.com/read/29266673/migratory-potential-of-transplanted-glial-progenitors-as-critical-factor-for-successful-translation-of-glia-replacement-therapy-the-gap-between-mice-and-men
#11
REVIEW
Rohit K Srivastava, Jeff W M Bulte, Piotr Walczak, Miroslaw Janowski
Neurological disorders are a major threat to public health. Stem cell-based regenerative medicine is now a promising experimental paradigm for its treatment, as shown in pre-clinical animal studies. Initial attempts have been on the replacement of neuronal cells only, but glial progenitors (GPs) are now becoming strong alternative cellular therapeutic candidates to replace oligodendrocytes and astrocytes as knowledge accumulates about their important emerging role in various disease processes. There are many examples of successful therapeutic outcomes for transplanted GPs in small animal models, but clinical translation has proved to be challenging due to the 1,000-fold larger volume of the human brain compared to mice...
December 20, 2017: Glia
https://www.readbyqxmd.com/read/29266405/constitutive-downregulation-protein-kinase-c-epsilon-in-hsod1g93a-astrocytes-influences-mglur5-signaling-and-the-regulation-of-glutamate-uptake
#12
Maxime Vergouts, Pierre J Doyen, Michael Peeters, Remi Opsomer, Emmanuel Hermans
Accumulating evidence indicates that motor neuron degeneration in amyotrophic lateral sclerosis (ALS) is a non-cell-autonomous process and that impaired glutamate clearance by astrocytes, leading to excitotoxicity, could participate in progression of the disease. In astrocytes derived from an animal model of ALS (hSOD1G93A rats), activation of type 5 metabotropic glutamate receptor (mGluR5) fails to increase glutamate uptake, impeding a putative dynamic neuroprotective mechanism involving astrocytes. Using astrocyte cultures from hSOD1G93A rats, we have demonstrated that the typical Ca2+ oscillations associated with mGluR5 activation were reduced, and that the majority of cells responded with a sustained elevation of intracellular Ca2+ concentration...
December 20, 2017: Glia
https://www.readbyqxmd.com/read/29230877/neonatal-mouse-cortical-but-not-isogenic-human-astrocyte-feeder-layers-enhance-the-functional-maturation-of-induced-pluripotent-stem-cell-derived-neurons-in-culture
#13
Fritz W Lischka, Anastasia Efthymiou, Qiong Zhou, Michael D Nieves, Nikki M McCormack, Matthew D Wilkerson, Gauthaman Sukumar, Clifton L Dalgard, Martin L Doughty
Human induced pluripotent stem (iPS) cell-derived neurons and astrocytes are attractive cellular tools for nervous system disease modeling and drug screening. Optimal utilization of these tools requires differentiation protocols that efficiently generate functional cell phenotypes in vitro. As nervous system function is dependent on networked neuronal activity involving both neuronal and astrocytic synaptic functions, we examined astrocyte effects on the functional maturation of neurons from human iPS cell-derived neural stem cells (NSCs)...
December 12, 2017: Glia
https://www.readbyqxmd.com/read/29226549/fasting-induces-astroglial-plasticity-in-the-olfactory-bulb-glomeruli-of-rats
#14
Virginie Daumas-Meyer, Gaëlle Champeil-Potokar, Catherine Chaumontet, Patrice Dahirel, Catherine Papillon, Patrice Congar, Isabelle Denis
The detection of food odors by the olfactory system, which plays a key role in regulating food intake and elaborating the hedonic value of food, is reciprocally influenced by the metabolic state. Fasting increases olfactory performance, notably by increasing the activity of olfactory bulb (OB) neurons. The glutamatergic synapses between olfactory sensory neurons and mitral cells in the OB glomeruli are regulated by astrocytes, periglomerular neurons, and centrifugal afferents. We compared the expansion of astroglial processes by quantifying GFAP-labeled areas in fed and fasted rats to see whether OB glomerular astrocytes are involved in the metabolic sensing and adaptation of the olfactory system...
December 11, 2017: Glia
https://www.readbyqxmd.com/read/29226424/activation-of-ep2-receptor-suppresses-poly-i-c-and-lps-mediated-inflammation-in-primary-microglia-and-organotypic-hippocampal-slice-cultures-contributing-role-for-mapks
#15
Nizar M Yousif, Antonio Carlos Pinheiro de Oliveira, Simone Brioschi, Michael Huell, Knut Biber, Bernd L Fiebich
Brain inflammation is a critical factor involved in neurodegeneration. Recently, the prostaglandin E2 (PGE2 ) downstream members were suggested to modulate neuroinflammatory responses accompanying neurodegenerative diseases. In this study, we investigated the protective effects of prostaglandin E2 receptor 2 (EP2 ) during TLR3 and TLR4-driven inflammatory response using in vitro primary microglia and ex vivo organotypic hippocampal slice cultures (OHSCs). Depletion of microglia from OHSCs differentially affected TLR3 and TLR4 receptor expression...
December 11, 2017: Glia
https://www.readbyqxmd.com/read/29222871/myelin-extracellular-leaflet-compaction-requires-apolipoprotein-d-membrane-management-to-optimize-lysosomal-dependent-recycling-and-glycocalyx-removal
#16
Nadia García-Mateo, Raquel Pascua-Maestro, Alberto Pérez-Castellanos, Concepción Lillo, Diego Sanchez, Maria D Ganfornina
To compact the extracellular sides of myelin, an important transition must take place: from membrane sliding, while building the wraps, to membrane adhesion and water exclusion. Removal of the negatively charged glycocalyx becomes the limiting factor in such transition. What is required to initiate this membrane-zipping process? Knocking-out the Lipocalin Apolipoprotein D (ApoD), essential for lysosomal functional integrity in glial cells, results in a specific defect in myelin extracellular leaflet compaction in peripheral and central nervous system, which results in reduced conduction velocity and suboptimal behavioral outputs: motor learning is compromised...
December 9, 2017: Glia
https://www.readbyqxmd.com/read/29219210/bioenergetic-regulation-of-microglia
#17
REVIEW
Soumitra Ghosh, Erika Castillo, Elma S Frias, Raymond A Swanson
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...
December 8, 2017: Glia
https://www.readbyqxmd.com/read/29214672/region-specific-deletions-of-the-glutamate-transporter-glt1-differentially-affect-seizure-activity-and-neurodegeneration-in-mice
#18
Junya Sugimoto, Moeko Tanaka, Kaori Sugiyama, Yukiko Ito, Hidenori Aizawa, Miho Soma, Tomoko Shimizu, Akira Mitani, Kohichi Tanaka
Glial glutamate transporter GLT1 plays a key role in the maintenance of extracellular glutamate homeostasis. Recent human genetic studies have suggested that de novo mutations in GLT1 (EAAT2) cause early-onset epilepsy with multiple seizure types. Consistent with these findings, global GLT1 null mice show lethal spontaneous seizures. The consequences of GLT1 dysfunction vary between different brain regions, suggesting that the role of GLT1 dysfunction in epilepsy may also vary with brain regions. 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...
December 6, 2017: Glia
https://www.readbyqxmd.com/read/29210103/myelination-and-mtor
#19
REVIEW
Gianluca Figlia, Daniel Gerber, Ueli Suter
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...
December 6, 2017: Glia
https://www.readbyqxmd.com/read/29193293/functional-antagonism-of-sphingosine-1-phosphate-receptor-1-prevents-cuprizone-induced-demyelination
#20
SunJa Kim, Jacek Bielawski, Hyunmin Yang, Yu Kong, Beiyan Zhou, Jianrong Li
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 oligodendrocytes and demyelination...
November 29, 2017: Glia
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