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https://www.readbyqxmd.com/read/29165835/the-function-of-contactin-2-tag-1-in-oligodendrocytes-in-health-and-demyelinating-pathology
#1
Lida Zoupi, Maria Savvaki, Katerina Kalemaki, Ilias Kalafatakis, Kyriaki Sidiropoulou, Domna Karagogeos
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 involvement on oligodendrocyte maturation, branching, myelin-gene expression, myelination, and axonal function...
November 22, 2017: Glia
https://www.readbyqxmd.com/read/29148104/neuregulin-1-promotes-remyelination-and-fosters-a-pro-regenerative-inflammatory-response-in-focal-demyelinating-lesions-of-the-spinal-cord
#2
Hardeep Kataria, Arsalan Alizadeh, Ghazaleh M Shahriary, Shekoofeh Saboktakin Rizi, Ryan Henrie, Kallivalappil T Santhosh, James A Thliveris, Soheila Karimi-Abdolrezaee
Oligodendroglial cell death and demyelination are hallmarks of neurotrauma and multiple sclerosis that cause axonal damage and functional impairments. Remyelination remains a challenge as the ability of endogenous precursor cells for oligodendrocyte replacement is hindered in the unfavorable milieu of demyelinating conditions. Here, in a rat model of lysolecithin lysophosphatidyl-choline (LPC)-induced focal demyelination, we report that Neuregulin-1 (Nrg-1), an important factor for oligodendrocytes and myelination, is dysregulated in demyelinating lesions and its bio-availability can promote oligodendrogenesis and remyelination...
November 17, 2017: Glia
https://www.readbyqxmd.com/read/29143372/a-critical-role-of-trpm2-channel-in-a%C3%AE-42-induced-microglial-activation-and-generation-of-tumor-necrosis-factor-%C3%AE
#3
Sharifah Alawieyah Syed Mortadza, Joan A Sim, Veronika E Neubrand, Lin-Hua Jiang
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...
November 16, 2017: Glia
https://www.readbyqxmd.com/read/29139169/sex-differences-in-the-phagocytic-and-migratory-activity-of-microglia-and-their-impairment-by-palmitic-acid
#4
Natalia Yanguas-Casás, Andrea Crespo-Castrillo, Maria L de Ceballos, Julie A Chowen, Iñigo Azcoitia, Maria Angeles Arevalo, Luis M Garcia-Segura
Sex differences in the incidence, clinical manifestation, disease course, and prognosis of neurological diseases, such as autism spectrum disorders or Alzheimer's disease, have been reported. Obesity has been postulated as a risk factor for cognitive decline and Alzheimer's disease and, during pregnancy, increases the risk of autism spectrum disorders in the offspring. Obesity is associated with increased serum and brain levels of free fatty acids, such as palmitic acid, which activate microglial cells triggering a potent inflammatory cascade...
November 15, 2017: Glia
https://www.readbyqxmd.com/read/29134703/origin-and-dynamics-of-oligodendrocytes-in-the-developing-brain-implications-for-perinatal-white-matter-injury
#5
REVIEW
Erik van Tilborg, Caroline G M de Theije, Maurik van Hal, Nienke Wagenaar, Linda S de Vries, Manon J Benders, David H Rowitch, Cora H Nijboer
Infants born prematurely are at high risk to develop white matter injury (WMI), due to exposure to hypoxic and/or inflammatory insults. Such perinatal insults negatively impact the maturation of oligodendrocytes (OLs), thereby causing deficits in myelination. To elucidate the precise pathophysiology underlying perinatal WMI, it is essential to fully understand the cellular mechanisms contributing to healthy/normal white matter development. OLs are responsible for myelination of axons. During brain development, OLs are generally derived from neuroepithelial zones, where neural stem cells committed to the OL lineage differentiate into OL precursor cells (OPCs)...
November 14, 2017: Glia
https://www.readbyqxmd.com/read/29134693/microglia-from-offspring-of-dams-with-allergic-asthma-exhibit-epigenomic-alterations-in-genes-dysregulated-in-autism
#6
Annie Vogel Ciernia, Milo Careaga, Janine M LaSalle, Paul Ashwood
Dysregulation in immune responses during pregnancy increases the risk of a having a child with an autism spectrum disorder (ASD). Asthma is one of the most common chronic diseases among pregnant women, and symptoms often worsen during pregnancy. We recently developed a mouse model of maternal allergic asthma (MAA) that induces changes in sociability, repetitive, and perseverative behaviors in the offspring. Since epigenetic changes help a static genome adapt to the maternal environment, activation of the immune system may epigenetically alter fetal microglia, the brain's resident immune cells...
November 14, 2017: Glia
https://www.readbyqxmd.com/read/29134678/systemic-immune-checkpoint-blockade-with-anti-pd1-antibodies-does-not-alter-cerebral-amyloid-%C3%AE-burden-in-several-amyloid-transgenic-mouse-models
#7
Martine Latta-Mahieu, Bradford Elmer, Alexis Bretteville, Yaming Wang, Mati Lopez-Grancha, Philippe Goniot, Nicolas Moindrot, Paul Ferrari, Véronique Blanc, Nathalie Schussler, Emmanuel Brault, Valérie Roudières, Véronique Blanchard, Zhi-Yong Yang, Pascal Barneoud, Philippe Bertrand, Bart Roucourt, Sofie Carmans, Astrid Bottelbergs, Liesbeth Mertens, Cindy Wintmolders, Peter Larsen, Caroline Hersley, Tyler McGathey, Margaret M Racke, Ling Liu, Jirong Lu, Michael J O'Neill, David R Riddell, Andreas Ebneth, Gary J Nabel, Laurent Pradier
Chronic inflammation represents a central component in the pathogenesis of Alzheimer's disease (AD). Recent work suggests that breaking immune tolerance by Programmed cell Death-1 (PD1) checkpoint inhibition produces an IFN-γ-dependent systemic immune response, with infiltration of the brain by peripheral myeloid cells and neuropathological as well as functional improvements even in mice with advanced amyloid pathology (Baruch et al., (): Nature Medicine, 22:135-137). Immune checkpoint inhibition was therefore suggested as potential treatment for neurodegenerative disorders when activation of the immune system is appropriate...
November 14, 2017: Glia
https://www.readbyqxmd.com/read/29124786/schwann-cell-precursors-in-health-and-disease
#8
REVIEW
Jorge B Aquino, Romina Sierra
Schwann cell precursors (SCPs) are frequently regarded as neural crest-derived cells (NCDCs) found in contact with axons during nerve formation. Nevertheless, cells with SCPs properties can be found up to the adulthood. They are well characterized with regard to both gene expression profile and cellular behavior -for instance, proliferation, migratory capabilities and survival requirements-. They differ in origin regarding their anatomic location: even though most of them are derived from migratory NCCs, there is also contribution of the boundary cap neural crest cells (bNCCs) to the skin and other tissues...
November 10, 2017: Glia
https://www.readbyqxmd.com/read/29120073/astrocytic-and-neuronal-oxidative-metabolism-are-coupled-to-the-rate-of-glutamate-glutamine-cycle-in-the-tree-shrew-visual-cortex
#9
Sarah Sonnay, Jordan Poirot, Nathalie Just, Anne-Catherine Clerc, Rolf Gruetter, Gregor Rainer, João M N Duarte
Astrocytes play an important role in glutamatergic neurotransmission, namely by clearing synaptic glutamate and converting it into glutamine that is transferred back to neurons. The rate of this glutamate-glutamine cycle (VNT ) has been proposed to couple to that of glucose utilization and of neuronal tricarboxylic acid (TCA) cycle. In this study, we tested the hypothesis that glutamatergic neurotransmission is also coupled to the TCA cycle rate in astrocytes. For that we investigated energy metabolism by means of magnetic resonance spectroscopy (MRS) in the primary visual cortex of tree shrews (Tupaia belangeri) under light isoflurane anesthesia at rest and during continuous visual stimulation...
November 9, 2017: Glia
https://www.readbyqxmd.com/read/29119608/synthetic-aav-crispr-vectors-for-blocking-hiv-1-expression-in-persistently-infected-astrocytes
#10
Christine Kunze, Kathleen Börner, Eike Kienle, Tanja Orschmann, Ejona Rusha, Martha Schneider, Milena Radivojkov-Blagojevic, Micha Drukker, Sabrina Desbordes, Dirk Grimm, Ruth Brack-Werner
Astrocytes, the most abundant cells in the mammalian brain, perform key functions and are involved in several neurodegenerative diseases. The human immunodeficiency virus (HIV) can persist in astrocytes, contributing to the HIV burden and neurological dysfunctions in infected individuals. While a comprehensive approach to HIV cure must include the targeting of HIV-1 in astrocytes, dedicated tools for this purpose are still lacking. Here we report a novel Adeno-associated virus-based vector (AAV9P1) with a synthetic surface peptide for transduction of astrocytes...
November 9, 2017: Glia
https://www.readbyqxmd.com/read/29110344/current-technical-approaches-to-brain-energy-metabolism
#11
REVIEW
L Felipe Barros, Juan P Bolaños, Gilles Bonvento, Anne-Karine Bouzier-Sore, Angus Brown, Johannes Hirrlinger, Sergey Kasparov, Frank Kirchhoff, Anne N Murphy, Luc Pellerin, Michael B Robinson, Bruno Weber
Neuroscience is a technology-driven discipline and brain energy metabolism is no exception. Once satisfied with mapping metabolic pathways at organ level, we are now looking to learn what it is exactly that metabolic enzymes and transporters do and when, where do they reside, how are they regulated, and how do they relate to the specific functions of neurons, glial cells, and their subcellular domains and organelles, in different areas of the brain. Moreover, we aim to quantify the fluxes of metabolites within and between cells...
November 7, 2017: Glia
https://www.readbyqxmd.com/read/29105869/downregulation-of-spinal-astrocytic-connexin43-leads-to-upregulation-of-interleukin-6-and-cyclooxygenase-2-and-mechanical-hypersensitivity-in-mice
#12
Norimitsu Morioka, Shiori Fujii, Syun Kondo, Fang Fang Zhang, Kazuki Miyauchi, Yoki Nakamura, Kazue Hisaoka-Nakashima, Yoshihiro Nakata
Connexin43 (Cx43), involved in intercellular signaling, is expressed in spinal dorsal horn astrocytes and crucial in the maintenance of neuropathic pain. Downregulation of spinal astrocytic Cx43 in mice enhances glutamatergic neurotransmission by decreasing glutamate transporter GLT-1 expression, resulting in cutaneous hypersensitivity. Decreased expression of astrocytic Cx43 could lead to altered expression of other nociceptive molecules. Transfection of Cx43-targeting siRNA in cultured spinal astrocytes increased expression of the pronociceptive cytokine interleukin-6 (IL-6) and the prostaglandin synthesizing enzyme cyclooxygenase-2 (COX-2)...
November 6, 2017: Glia
https://www.readbyqxmd.com/read/29105838/a-parkinson-s-disease-gene-dj-1-repairs-brain-injury-through-sox9-stabilization-and-astrogliosis
#13
Dong-Joo Choi, Jin-Hwa Eun, Byung Gon Kim, Ilo Jou, Sang Myun Park, Eun-Hye Joe
Defects in repair of damaged brain accumulate injury and contribute to slow-developing neurodegeneration. Here, we report that a deficiency of DJ-1, a Parkinson's disease (PD) gene, delays repair of brain injury due to destabilization of Sox9, a positive regulator of astrogliosis. Stereotaxic injection of ATP into the brain striatum produces similar size of acute injury in wild-type and DJ-1-knockout (KO) mice. However, recovery of the injury is delayed in KO mice, which is confirmed by 9.4T magnetic resonance imaging and tyrosine hydroxylase immunostaining...
November 6, 2017: Glia
https://www.readbyqxmd.com/read/29098734/regulation-of-mitochondrial-dynamics-in-astrocytes-mechanisms-consequences-and-unknowns
#14
Joshua G Jackson, Michael B Robinson
Astrocytes are the major glial cell in the central nervous system. These polarized cells possess numerous processes that ensheath the vasculature and contact synapses. Astrocytes play important roles in synaptic signaling, neurotransmitter synthesis and recycling, control of nutrient uptake, and control of local blood flow. Many of these processes depend on local metabolism and/or energy utilization. While astrocytes respond to increases in neuronal activity and metabolic demand by upregulating glycolysis and glycogenolysis, astrocytes also possess significant capacity for oxidative (mitochondrial) metabolism...
November 3, 2017: Glia
https://www.readbyqxmd.com/read/29086442/kallikrein-6-secreted-by-oligodendrocytes-regulates-the-progression-of-experimental-autoimmune-encephalomyelitis
#15
Yoshio Bando, Yoshiaki Hagiwara, Yasuhiro Suzuki, Kosuke Yoshida, Yoko Aburakawa, Takashi Kimura, Chisato Murakami, Miyuki Ono, Tatsuhide Tanaka, Ying-Ping Jiang, Branka Mitrovi, Hiroki Bochimoto, Osamu Yahara, Shigetaka Yoshida
Multiple sclerosis (MS) is an inflammatory demyelinating disease of the central nervous system (CNS), and experimental autoimmune encephalomyelitis (EAE) is a well-established animal model of the disease. Here, we examined the pathophysiological role of Kallikrein 6 (Klk6), a serine protease produced by oligodendrocytes (OLs), in EAE using Klk6 knockout (Klk6-/-) mice. Compared with Klk6+/+ (wild-type) mice, Klk6-/- mice showed milder EAE symptoms, including delayed onset and milder paralysis. Loss of Klk6 suppressed matrix metalloprotease-9 expression and diminished the infiltration of peripheral inflammatory cells into the CNS by decreasing blood-brain barrier (BBB) permeability and reducing expression levels of inflammatory cytokines, chemokines and their receptors...
October 31, 2017: Glia
https://www.readbyqxmd.com/read/29076603/astrocyte-glycogen-and-lactate-new-insights-into-learning-and-memory-mechanisms
#16
Cristina M Alberini, Emmanuel Cruz, Giannina Descalzi, Benjamin Bessières, Virginia Gao
Memory, the ability to retain learned information, is necessary for survival. Thus far, molecular and cellular investigations of memory formation and storage have mainly focused on neuronal mechanisms. In addition to neurons, however, the brain comprises other types of cells and systems, including glia and vasculature. Accordingly, recent experimental work has begun to ask questions about the roles of non-neuronal cells in memory formation. These studies provide evidence that all types of glial cells (astrocytes, oligodendrocytes, and microglia) make important contributions to the processing of encoded information and storing memories...
October 27, 2017: Glia
https://www.readbyqxmd.com/read/29076578/impairment-of-protein-degradation-and-proteasome-function-in-hereditary-neuropathies
#17
Jordan J S VerPlank, Sudarsanareddy Lokireddy, M Laura Feltri, Alfred L Goldberg, Lawrence Wrabetz
In several neurodegenerative diseases in which misfolded proteins accumulate there is impairment of the ubiquitin proteasome system (UPS). We tested if a similar disruption of proteostasis occurs in hereditary peripheral neuropathies. In sciatic nerves from mouse models of two human neuropathies, Myelin Protein Zero mutation (S63del) and increased copy number (P0 overexpression), polyubiquitinated proteins accumulated, and the overall rates of protein degradation were decreased. 26S proteasomes affinity-purified from sciatic nerves of S63del mice were defective in degradation of peptides and a ubiquitinated protein, unlike proteasomes from P0 overexpression, which appeared normal...
October 27, 2017: Glia
https://www.readbyqxmd.com/read/29076551/tgf-%C3%AE-pro-oligodendrogenic-effects-on-adult-svz-progenitor-cultures-and-its-interaction-with-the-notch-signaling-pathway
#18
Laura I Gómez Pinto, Debora Rodríguez, Ana M Adamo, Patricia A Mathieu
Adult neural progenitor cells (NPCs) are capable of differentiating into neurons, astrocytes, and oligodendrocytes throughout life. Notch and transforming growth factor β1 (TGF-β) signaling pathways play critical roles in controlling these cell fate decisions. TGF-β has been previously shown to exert pro-neurogenic effects on hippocampal and subventricular zone (SVZ) NPCs in vitro and to interact with Notch in different cellular types. Therefore, the aim of our work was to study the effect of TGF-β on adult rat brain SVZ NPC glial commitment and its interaction with Notch signaling...
October 27, 2017: Glia
https://www.readbyqxmd.com/read/29068088/mechanisms-of-lysophosphatidylcholine-induced-demyelination-a-primary-lipid-disrupting-myelinopathy
#19
Jason R Plemel, Nathan J Michaels, Nina Weishaupt, Andrew V Caprariello, Michael B Keough, James A Rogers, Aran Yukseloglu, Jaehyun Lim, Vikas V Patel, Khalil S Rawji, Samuel K Jensen, Wulin Teo, Belinda Heyne, Shawn N Whitehead, Peter K Stys, V Wee Yong
For decades lysophosphatidylcholine (LPC, lysolecithin) has been used to induce demyelination, without a clear understanding of its mechanisms. LPC is an endogenous lysophospholipid so it may cause demyelination in certain diseases. We investigated whether known receptor systems, inflammation or nonspecific lipid disruption mediates LPC-demyelination in mice. We found that LPC nonspecifically disrupted myelin lipids. LPC integrated into cellular membranes and rapidly induced cell membrane permeability; in mice, LPC injury was phenocopied by other lipid disrupting agents...
October 25, 2017: Glia
https://www.readbyqxmd.com/read/29058362/the-ketone-body-metabolite-%C3%AE-hydroxybutyrate-induces-an-antidepression-associated-ramification-of-microglia-via-hdacs-inhibition-triggered-akt-small-rhogtpase-activation
#20
Chao Huang, Peng Wang, Xing Xu, Yaru Zhang, Yu Gong, Wenfeng Hu, Minhui Gao, Yue Wu, Yong Ling, Xi Zhao, Yibin Qin, Rongrong Yang, Wei Zhang
Direct induction of macrophage ramification has been shown to promote an alternative (M2) polarization, suggesting that the ramified morphology may determine the function of immune cells. The ketone body metabolite β-hydroxybutyrate (BHB) elevated in conditions including fasting and low-carbohydrate ketogenic diet (KD) can reduce neuroinflammation. However, how exactly BHB impacts microglia remains unclear. We report that BHB as well as its producing stimuli fasting and KD induced obvious ramifications of murine microglia in basal and inflammatory conditions in a reversible manner, and these ramifications were accompanied with microglial profile toward M2 polarization and phagocytosis...
October 23, 2017: Glia
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