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Myelination microglia

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https://www.readbyqxmd.com/read/28783571/a-novel-flavanone-derivative-ameliorates-cuprizone-induced-behavioral-changes-and-white-matter-pathology-in-the-brain-of-mice
#1
Zheng-Yu Sun, Hong-Shun Gu, Xi Chen, Lan Zhang, Xin-Min Li, Jian-Wei Zhang, Lin Li
Recent studies have shown that white matter lesions play an important role in the pathogenesis of schizophrenia. DHF-6 is a novel flavanone derivative synthesized in our laboratory. The purpose of the present study was to investigate the effects of DHF-6 on behavioral changes and white matter pathology in a 0.2% cuprizone-fed C57BL/6 mice model. The results showed that cuprizone induced a decrease in spontaneous alternations in the Y-maze test, an increase in locomotor activity in the open field test, demyelination determined by electron microscopy, a decline in the expression of myelin basic protein (MBP), a decrease in the differentiation of oligodendrocyte precursor cells (OPCs) into mature oligodendrocytes (OLs), and an activation of microglia and astrocytes in the corpus callosum measured by western blot and/or immunocytochemical analyses...
July 31, 2017: Psychiatry Research
https://www.readbyqxmd.com/read/28776122/mechanisms-involved-in-the-remyelinating-effect-of-sildenafil
#2
Daniela Díaz-Lucena, María Gutierrez-Mecinas, Beatriz Moreno, José Lupicinio Martínez-Sánchez, Paula Pifarré, Agustina García
Remyelination occurs in demyelinated lesions in multiple sclerosis (MS) and pharmacological treatments that enhance this process will critically impact the long term functional outcome in the disease. Sildenafil, a cyclic GMP (cGMP)-specific phosphodiesterase 5 inhibitor (PDE5-I), is an oral vasodilator drug extensively used in humans for treatment of erectile dysfunction and pulmonary arterial hypertension. PDE5 is expressed in central nervous system (CNS) neuronal and glial populations and in endothelial cells and numerous studies in rodent models of neurological disease have evidenced the neuroprotective potential of PDE5-Is...
August 3, 2017: Journal of Neuroimmune Pharmacology: the Official Journal of the Society on NeuroImmune Pharmacology
https://www.readbyqxmd.com/read/28762472/absence-of-notch1-in-murine-myeloid-cells-attenuates-the-development-of-experimental-autoimmune-encephalomyelitis-by-affecting-th1-and-th17-priming
#3
Miriam Fernández, Eva M Monsalve, Susana López-López, Almudena Ruiz-García, Susana Mellado, Elena Caminos, José Javier García-Ramírez, Jorge Laborda, Pedro Tranque, María José M Díaz-Guerra
Inhibition of Notch signalling in T cells attenuates the development of experimental autoimmune encephalomyelitis (EAE), a mouse model of multiple sclerosis. Growing evidence indicates that myeloid cells are also key players in autoimmune processes. Thus, the present study evaluates the role of the Notch1 receptor in myeloid cells on the progression of myelin oligodendrocyte glycoprotein (MOG)35-55 -induced EAE, using mice with a myeloid-specific deletion of the Notch1 gene (MyeNotch1KO). We found that EAE progression was less severe in the absence of Notch1 in myeloid cells...
August 1, 2017: European Journal of Immunology
https://www.readbyqxmd.com/read/28744286/a-b-cell-driven-autoimmune-pathway-leading-to-pathological-hallmarks-of-progressive-multiple-sclerosis-in-the-marmoset-experimental-autoimmune-encephalomyelitis-model
#4
REVIEW
Bert A 't Hart, Jordon Dunham, Bart W Faber, Jon D Laman, Jack van Horssen, Jan Bauer, Yolanda S Kap
The absence of pathological hallmarks of progressive multiple sclerosis (MS) in commonly used rodent models of experimental autoimmune encephalomyelitis (EAE) hinders the development of adequate treatments for progressive disease. Work reviewed here shows that such hallmarks are present in the EAE model in marmoset monkeys (Callithrix jacchus). The minimal requirement for induction of progressive MS pathology is immunization with a synthetic peptide representing residues 34-56 from human myelin oligodendrocyte glycoprotein (MOG) formulated with a mineral oil [incomplete Freund's adjuvant (IFA)]...
2017: Frontiers in Immunology
https://www.readbyqxmd.com/read/28738878/tlr4-response-mediates-ethanol-induced-neurodevelopment-alterations-in-a-model-of-fetal-alcohol-spectrum-disorders
#5
María Pascual, Jorge Montesinos, Sandra Montagud-Romero, Jerónimo Forteza, Marta Rodríguez-Arias, José Miñarro, Consuelo Guerri
BACKGROUND: Inflammation during brain development participates in the pathogenesis of early brain injury and cognitive dysfunctions. Prenatal ethanol exposure affects the developing brain and causes neural impairment, cognitive and behavioral effects, collectively known as fetal alcohol spectrum disorders (FASD). Our previous studies demonstrate that ethanol activates the innate immune response and TLR4 receptor and causes neuroinflammation, brain damage, and cognitive defects in the developmental brain stage of adolescents...
July 24, 2017: Journal of Neuroinflammation
https://www.readbyqxmd.com/read/28736137/nogo-presence-is-inversely-associated-with-shifts-in-cortical-microglial-morphology-following-experimental-diffuse-brain-injury
#6
Jenna M Ziebell, Helen Ray-Jones, Jonathan Lifshitz
Diffuse traumatic brain injury (TBI) initiates secondary pathology, including inflammation and reduced myelination. Considering these injury-related pathologies, the many states of activated microglia as demonstrated by differing morphologies would form, migrate, and function in and through fields of growth-inhibitory myelin byproduct, specifically Nogo. Here we evaluate the relationship between inflammation and reduced myelin antigenicity in the wake of diffuse TBI and present the hypothesis that the Nogo-66 receptor antagonist peptide NEP(1-40) would reverse the injury-induced shift in distribution of microglia morphologies by limiting myelin-based inhibition...
July 20, 2017: Neuroscience
https://www.readbyqxmd.com/read/28730968/modulation-of-the-immune-system-for-the-treatment-of-glaucoma
#7
Katharina Bell, Nadine von Thun Und Hohenstein-Blaul, Julia Teister, Franz H Grus
At present intraocular pressure (IOP) lowering therapies are the only approach to treat glaucoma. Neuroprotective strategies to protect the retinal ganglion cells (RGC) from apoptosis are lacking to date. Results from clinical studies revealed altered immunoreactivities against retinal and optic nerve antigens in sera and aqueous humor of glaucoma patients and point toward an autoimmune involvement in glaucomatous neurodegeneration and RGC death. IgG accumulations along with plasma cells were found localised in human glaucomatous retinae in a pro-inflammatory environment possibly maintained by microglia...
July 19, 2017: Current Neuropharmacology
https://www.readbyqxmd.com/read/28727115/the-microbiota-gut-brain-axis-as-a-key-regulator-of-neural-function-and-the-stress-response-implications-for-human-and-animal-health
#8
N C Wiley, T G Dinan, R P Ross, C Stanton, G Clarke, J F Cryan
The brain-gut-microbiota axis comprises an extensive communication network between the brain, the gut, and the microbiota residing there. Development of a diverse gut microbiota is vital for multiple features of behavior and physiology, as well as many fundamental aspects of brain structure and function. Appropriate early-life assembly of the gut microbiota is also believed to play a role in subsequent emotional and cognitive development. If the composition, diversity, or assembly of the gut microbiota is impaired, this impairment can have a negative impact on host health and lead to disorders such as obesity, diabetes, inflammatory diseases, and even potentially neuropsychiatric illnesses, including anxiety and depression...
July 2017: Journal of Animal Science
https://www.readbyqxmd.com/read/28722234/minocycline-reduces-microgliosis-and-improves-subcortical-white-matter-function-in-a-model-of-cerebral-vascular-disease
#9
Yasmina Manso, Philip R Holland, Akihiro Kitamura, Stefan Szymkowiak, Jessica Duncombe, Edel Hennessy, James L Searcy, Martina Marangoni, Andrew D Randall, Jon T Brown, Barry W McColl, Karen Horsburgh
Chronic cerebral hypoperfusion is a key mechanism associated with white matter disruption in cerebral vascular disease and dementia. In a mouse model relevant to studying cerebral vascular disease, we have previously shown that cerebral hypoperfusion disrupts axon-glial integrity and the distribution of key paranodal and internodal proteins in subcortical myelinated axons. This disruption of myelinated axons is accompanied by increased microglia and cognitive decline. The aim of the present study was to investigate whether hypoperfusion impairs the functional integrity of white matter, its relation with axon-glial integrity and microglial number, and whether by targeting microglia these effects can be improved...
July 19, 2017: Glia
https://www.readbyqxmd.com/read/28702713/the-role-of-the-oligodendrocyte-lineage-in-acute-brain-trauma
#10
Anja Scheller, Xianshu Bai, Frank Kirchhoff
An acute brain injury is commonly characterized by an extended cellular damage. The post-injury process of scar formation is largely determined by responses of various local glial cells and blood-derived immune cells. The role of astrocytes and microglia have been frequently reviewed in the traumatic sequelae. Here, we summarize the diverse contributions of oligodendrocytes (OLs) and their precursor cells (OPCs) in acute injuries. OLs at the lesion site are highly sensitive to a damaging insult, provoked by Ca(2+) overload after hyperexcitation originating from increased levels of transmitters...
July 12, 2017: Neurochemical Research
https://www.readbyqxmd.com/read/28696010/myelin-as-an-inflammatory-mediator-myelin-interactions-with-complement-macrophages-and-microglia-in-spinal-cord-injury
#11
REVIEW
Timothy J Kopper, John C Gensel
Spinal cord injury (SCI) triggers chronic intraspinal inflammation consisting of activated resident and infiltrating immune cells (especially microglia/macrophages). The environmental factors contributing to this protracted inflammation are not well understood; however, myelin lipid debris is a hallmark of SCI. Myelin is also a potent macrophage stimulus and target of complement-mediated clearance and inflammation. The downstream effects of these neuroimmune interactions have the potential to contribute to ongoing pathology or facilitate repair...
July 11, 2017: Journal of Neuroscience Research
https://www.readbyqxmd.com/read/28694451/polymorphic-regulation-of-mitochondrial-fission-and-fusion-modifies-phenotypes-of-microglia-in-neuroinflammation
#12
Mitsuhiko Katoh, Bao Wu, Huy Bang Nguyen, Truc Quynh Thai, Ryo Yamasaki, Haiyan Lu, Anna M Rietsch, Musab M Zorlu, Youichi Shinozaki, Yurika Saitoh, Sei Saitoh, Takashi Sakoh, Kazuhiro Ikenaka, Schuichi Koizumi, Richard M Ransohoff, Nobuhiko Ohno
Microglia are the resident macrophages of the central nervous system and play complex roles in the milieu of diseases including the primary diseases of myelin. Although mitochondria are critical for cellular functions and survival in the nervous system, alterations in and the roles of mitochondrial dynamics and associated signaling in microglia are still poorly understood. In the present study, by combining immunohistochemistry and 3D ultrastructural analyses, we show that mitochondrial fission/fusion in reactive microglia is differentially regulated from that in monocyte-derived macrophages and the ramified microglia of normal white matter in myelin disease models...
July 10, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28685323/microglia-contribute-to-normal-myelinogenesis-and-to-oligodendrocyte-progenitor-maintenance-during-adulthood
#13
Nora Hagemeyer, Klara-Maria Hanft, Maria-Anna Akriditou, Nicole Unger, Eun S Park, E Richard Stanley, Ori Staszewski, Leda Dimou, Marco Prinz
Whereas microglia involvement in virtually all brain diseases is well accepted their role in the control of homeostasis in the central nervous system (CNS) is mainly thought to be the maintenance of neuronal function through the formation, refinement, and monitoring of synapses in both the developing and adult brain. Although the prenatal origin as well as the neuron-centered function of cortical microglia has recently been elucidated, much less is known about a distinct amoeboid microglia population formerly described as the "fountain of microglia" that appears only postnatally in myelinated regions such as corpus callosum and cerebellum...
July 6, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28670274/differentially-severe-cognitive-effects-of-compromised-cerebral-blood-flow-in-aged-mice-association-with-myelin-degradation-and-microglia-activation
#14
Gilly Wolf, Amit Lotan, Tzuri Lifschytz, Hagar Ben-Ari, Tirzah Kreisel Merzel, Pavel Tatarskyy, Michael Valitzky, Ben Mernick, Elad Avidan, Nickolay Koroukhov, Bernard Lerer
Bilateral common carotid artery stenosis (BCAS) models the effects of compromised cerebral blood flow on brain structure and function in mice. We compared the effects of BCAS in aged (21 month) and young adult (3 month) female mice, anticipating a differentially more severe effect in the older mice. Four weeks after surgery there was a significant age by time by treatment interaction on the radial-arm water maze (RAWM; p = 0.014): on the first day of the test, latencies of old mice were longer compared to the latencies of young adult mice, independent of BCAS...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28638987/leukodystrophies-a-proposed-classification-system-based-on-pathological-changes-and-pathogenetic-mechanisms
#15
REVIEW
Marjo S van der Knaap, Marianna Bugiani
Leukodystrophies are genetically determined disorders characterized by the selective involvement of the central nervous system white matter. Onset may be at any age, from prenatal life to senescence. Many leukodystrophies are degenerative in nature, but some only impair white matter function. The clinical course is mostly progressive, but may also be static or even improving with time. Progressive leukodystrophies are often fatal, and no curative treatment is known. The last decade has witnessed a tremendous increase in the number of defined leukodystrophies also owing to a diagnostic approach combining magnetic resonance imaging pattern recognition and next generation sequencing...
June 21, 2017: Acta Neuropathologica
https://www.readbyqxmd.com/read/28629387/an-updated-assessment-of-microglia-depletion-current-concepts-and-future-directions
#16
REVIEW
Jinming Han, Robert A Harris, Xing-Mei Zhang
Microglia are the principal resident immune cells in the central nervous system and are believed to be versatile players in both inflammatory and physiological contexts. On the one hand, in order to safeguard the microenvironment microglia can be rapidly activated by contact with microbial products or cell debris, thereby exerting the functions of innate immunity via phagocytosis and secretion of cytokines and chemokines. Conversely, microglia can also assist in brain development, synaptic plasticity and neural repair through the production of neurotrophic factors and clearance of myelin debris...
June 19, 2017: Molecular Brain
https://www.readbyqxmd.com/read/28625767/early-life-stress-perturbs-the-function-of-microglia-in-the-developing-rodent-brain-new-insights-and-future-challenges
#17
REVIEW
Frances K Johnson, Arie Kaffman
The role of the innate immune system in mediating some of the consequences of childhood abuse and neglect has received increasing attention in recent years. Most of the work to date has focused on the role that neuroinflammation plays in the long-term adult psychiatric and medical complications associated with childhood maltreatment. The effects of stress-induced neuroinflammation on neurodevelopment have received little attention because until recently this issue has not been studied systematically in animal models of early life stress...
June 15, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28618115/iron-sulfur-glutaredoxin-2-protects-oligodendrocytes-against-damage-induced-by-nitric-oxide-release-from-activated-microglia
#18
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...
September 2017: Glia
https://www.readbyqxmd.com/read/28606007/dimethyl-fumarate-improves-white-matter-function-following-severe-hypoperfusion-involvement-of-microglia-macrophages-and-inflammatory-mediators
#19
Jill H Fowler, Jamie McQueen, Philip R Holland, Yasmina Manso, Martina Marangoni, Fiona Scott, Emma Chisholm, Robert H Scannevin, Giles E Hardingham, Karen Horsburgh
The brain's white matter is highly vulnerable to reductions in cerebral blood flow via mechanisms that may involve elevated microgliosis and pro-inflammatory pathways. In the present study, the effects of severe cerebral hypoperfusion were investigated on white matter function and inflammation. Male C57Bl/6J mice underwent bilateral common carotid artery stenosis and white matter function was assessed at seven days with electrophysiology in response to evoked compound action potentials (CAPs) in the corpus callosum...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28593439/clinical-and-histopathological-amelioration-of-experimental-autoimmune-encephalomyelitis-by-aav-vectors-expressing-a-soluble-interleukin-23-receptor
#20
Marta Miralles, Herena Eixarch, Marcos Tejero, Carme Costa, Keiji Hirota, A Raul Castaño, Meritxell Puig, Gitta Stockinger, Xavier Montalban, Assumpció Bosch, Carmen Espejo, Miguel Chillon
The role of the T helper (Th)17 pathway has been clearly demonstrated in the onset and progression of autoimmune diseases, where interleukin (IL)-23 is a key molecule in maintaining the response mediated by Th17 cells. As a consequence, recent strategies based on blocking the interaction between IL-23 and its receptor (IL-23R), for example the anti-p19 antibody tildrakizumab, have been developed to regulate the Th17 pathway from the initial stages of the disease. Here, a soluble (s)IL-23R cDNA was cloned in expression plasmids and viral vectors...
June 7, 2017: Neurotherapeutics: the Journal of the American Society for Experimental NeuroTherapeutics
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