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Microglia function

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https://www.readbyqxmd.com/read/28930663/the-trem2-apoe-pathway-drives-the-transcriptional-phenotype-of-dysfunctional-microglia-in-neurodegenerative-diseases
#1
Susanne Krasemann, Charlotte Madore, Ron Cialic, Caroline Baufeld, Narghes Calcagno, Rachid El Fatimy, Lien Beckers, Elaine O'Loughlin, Yang Xu, Zain Fanek, David J Greco, Scott T Smith, George Tweet, Zachary Humulock, Tobias Zrzavy, Patricia Conde-Sanroman, Mar Gacias, Zhiping Weng, Hao Chen, Emily Tjon, Fargol Mazaheri, Kristin Hartmann, Asaf Madi, Jason D Ulrich, Markus Glatzel, Anna Worthmann, Joerg Heeren, Bogdan Budnik, Cynthia Lemere, Tsuneya Ikezu, Frank L Heppner, Vladimir Litvak, David M Holtzman, Hans Lassmann, Howard L Weiner, Jordi Ochando, Christian Haass, Oleg Butovsky
Microglia play a pivotal role in the maintenance of brain homeostasis but lose homeostatic function during neurodegenerative disorders. We identified a specific apolipoprotein E (APOE)-dependent molecular signature in microglia from models of amyotrophic lateral sclerosis (ALS), multiple sclerosis (MS), and Alzheimer's disease (AD) and in microglia surrounding neuritic β-amyloid (Aβ)-plaques in the brains of people with AD. The APOE pathway mediated a switch from a homeostatic to a neurodegenerative microglia phenotype after phagocytosis of apoptotic neurons...
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28930654/a-tale-of-two-genes-microglial-apoe-and-trem2
#2
Anna A Pimenova, Edoardo Marcora, Alison M Goate
Microglial cell function is implicated in the etiology of Alzheimer's disease by human genetics. In this issue of Immunity, Krasemann et al. (2017) describe a gene expression signature associated with an APOE- and TREM2-dependent response of microglia to brain tissue damage that accumulates in aging and disease, defining an axis that might be amenable to therapeutic targeting.
September 19, 2017: Immunity
https://www.readbyqxmd.com/read/28929580/selective-expression-of-egfp-in-mouse-perivascular-astrocytes-by-modification-of-the-mlc1-gene-using-t2a-based-ribosome-skipping
#3
Jordan J Toutounchian, Joseph H McCarty
Perivascular astrocyte end feet closely juxtapose cerebral blood vessels to regulate important developmental and physiological processes including endothelial cell proliferation and sprouting as well as the formation of the blood-brain barrier (BBB). The mechanisms underlying these events remain largely unknown due to a lack of experimental models for identifying perivascular astrocytes and distinguishing these cell types from other astroglial populations. Megalencephalic leukoencephalopathy with subcortical cysts 1 (Mlc1) is a transmembrane protein that is expressed in perivascular astrocyte end feet where it controls BBB development and homeostasis...
September 20, 2017: Genesis: the Journal of Genetics and Development
https://www.readbyqxmd.com/read/28928406/hemoglobin-enhances-mirna-144-expression-and-autophagic-activation-mediated-inflammation-of-microglia-via-mtor-pathway
#4
Zhenyu Wang, Bangqing Yuan, Fenlan Fu, Shaokuan Huang, Zhao Yang
Intracerebral hemorrhage promotes autophagic activation of microglia and enhances neuroinflammation. MiRNAs are key factors to autophagy, contributed to negatively and posttranscriptionally regulate gene expression and function. However, the specific miRNAs involved in the intracerebral hemorrhage mediated microglia autophagic activation are unidentified. In this experiment, microglia was treated with hemoglobin. And then, miRNA-144 expression, autophagic activation and inflammation of microglia were detected...
September 19, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28928004/syncytin-1-an-endogenous-retroviral-protein-triggers-the-activation-of-crp-via-tlr3-signal-cascade-in-glial-cells
#5
Xiuling Wang, Zhongchun Liu, Peigang Wang, Shan Li, Jie Zeng, Xiaoning Tu, Qiujin Yan, Zheman Xiao, Mengxian Pan, Fan Zhu
Schizophrenia is a devastating psychiatric disorder that impacts on social functioning and quality of life, and there is accumulating evidence that inflammation is a potential pathogenic mechanism of schizophrenia. However, the mechanism of inflammation possibly occurred in schizophrenia has not been well understood. The endogenous retroviral protein syncytin-1 and inflammatory marker CRP are both abnormally expressed in schizophrenia patients. CRP is one of the markers of bacterial infection generally. Less clear is whether virus or viral protein can trigger the activation of CRP...
September 16, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28925578/combined-fetal-inflammation-and-postnatal-hypoxia-causes-myelin-deficits-and-autism-like-behavior-in-a-rat-model-of-diffuse-white-matter-injury
#6
Erik van Tilborg, E J Marijke Achterberg, Caren M van Kammen, Annette van der Toorn, Floris Groenendaal, Rick M Dijkhuizen, Cobi J Heijnen, Louk J M J Vanderschuren, Manon N J L Benders, Cora H A Nijboer
Diffuse white matter injury (WMI) is a serious problem in extremely preterm infants, and is associated with adverse neurodevelopmental outcome, including cognitive impairments and an increased risk of autism-spectrum disorders. Important risk factors include fetal or perinatal inflammatory insults and fluctuating cerebral oxygenation. However, the exact mechanisms underlying diffuse WMI are not fully understood and no treatment options are currently available. The use of clinically relevant animal models is crucial to advance knowledge on the pathophysiology of diffuse WMI, allowing the definition of novel therapeutic targets...
September 19, 2017: Glia
https://www.readbyqxmd.com/read/28925510/mir-30a-5p-ameliorates-spinal-cord-injury-induced-inflammatory-responses-and-oxidative-stress-by-targeting-neurod-1-through-mapk-erk-signaling
#7
Xiaodong Fu, Yi Shen, Weili Wang, Xiaomiao Li
Spinal cord injury (SCI) is a major disability requiring more effective treatment than is currently available. MicroRNAs have been shown to effectively regulate gene expression at the translational level. The aim of the present study was to explore the potential role of miR-30-5p and possible mechanism in SCI. We found that miR-30-5p was notably down-regulated, while Neurod 1 expression was highly elevated in microglia from the mouse model of SCI. Additionally, overexpression of miR-30a-5p significantly suppressed inflammatory responses as reflected by an decrease in the secretion of the cytokines TNF-α, IL-1β and IL-10 triggered by SCI...
September 19, 2017: Clinical and Experimental Pharmacology & Physiology
https://www.readbyqxmd.com/read/28924548/remodeling-the-blood-brain-barrier-microenvironment-by-natural-products-for-brain-tumor-therapy
#8
REVIEW
Xiao Zhao, Rujing Chen, Mei Liu, Jianfang Feng, Jun Chen, Kaili Hu
Brain tumor incidence shows an upward trend in recent years; brain tumors account for 5% of adult tumors, while in children, this figure has increased to 70%. Moreover, 20%-30% of malignant tumors will eventually metastasize into the brain. Both benign and malignant tumors can cause an increase in intracranial pressure and brain tissue compression, leading to central nervous system (CNS) damage which endangers the patients' lives. Despite the many approaches to treating brain tumors and the progress that has been made, only modest gains in survival time of brain tumor patients have been achieved...
September 2017: Acta Pharmaceutica Sinica. B
https://www.readbyqxmd.com/read/28924145/a-novel-mouse-model-of-traumatic-optic-neuropathy-using-external-ultrasound-energy-to-achieve-focal-indirect-optic-nerve-injury
#9
Wensi Tao, Galina Dvoriantchikova, Brian C Tse, Steven Pappas, Tsung-Han Chou, Manuel Tapia, Vittorio Porciatti, Dmitry Ivanov, David T Tse, Daniel Pelaez
Traumatic optic neuropathy (TON) is a devastating cause of permanent visual loss following blunt injury to the head. Animal models for TON exist, but most fail to recapitulate the clinical scenario of closed head indirect trauma to the nerve and subsequent neurodegeneration. Thus, we developed a clinically-relevant animal model for TON using a novel ultrasonic pulse injury modality (sonication-induced TON; SI-TON). To trigger TON, a microtip probe sonifier was placed on the supraorbital ridge directly above the entrance of the optic nerve into the bony canal...
September 18, 2017: Scientific Reports
https://www.readbyqxmd.com/read/28924010/microrna-1906-a-novel-regulator-of-toll-like-receptor-4-ameliorates-ischemic-injury-after-experimental-stroke-in-mice
#10
Xiaomeng Xu, Zhuoyu Wen, Nan Zhao, Xiaohui Xu, Fang Wang, Jie Gao, Yongjun Jiang, Xinfeng Liu
Toll-like receptor 4 (TLR4) is a pro-inflammatory cascade initiator in post-stroke inflammation. In this study, miR-1906, a novel regulator of TLR4, was identified via in silico analysis and microRNA profiling in male adult mice, and its expression was then quantitated in the ischemic hemisphere. We found miR-1906 to be significantly brain-enriched in the ischemic hemisphere and even more drastically enriched in the peri-infarct regions. Furthermore, in vitro experiments demonstrated that during oxygen-glucose deprivation (OGD), miR-1906 expression was increased in glial cells but decreased in neurons...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28924009/site-specific-regulation-of-p2x7-receptor-function-in-microglia-gates-morphine-analgesic-tolerance
#11
Heather Leduc-Pessah, Nicholas L Weilinger, Churmy Y Fan, Nicole E Burma, Roger J Thompson, Tuan Trang
Tolerance to the analgesic effects of opioids is a major problem in chronic pain management. Microglia are implicated in opioid tolerance, but the core mechanisms regulating their response to opioids remain obscure. By selectively ablating microglia in the spinal cord using a saporin-conjugated antibody to Mac1, we demonstrate a causal role for microglia in the development, but not maintenance, of morphine tolerance in male rats. Increased P2X7 receptor (P2X7R) activity is a cardinal feature of microglial activation, and in this study we found that morphine potentiates P2X7R-mediated Ca(2+) responses in resident spinal microglia acutely isolated from morphine tolerant rats...
September 18, 2017: Journal of Neuroscience: the Official Journal of the Society for Neuroscience
https://www.readbyqxmd.com/read/28923916/critical-role-of-caveolin-1-in-ocular-neovascularization-and-multitargeted-antiangiogenic-effects-of-cavtratin-via-jnk
#12
Yida Jiang, Xianchai Lin, Zhongshu Tang, Chunsik Lee, Geng Tian, Yuxiang Du, Xiangke Yin, Xiangrong Ren, Lijuan Huang, Zhimin Ye, Wei Chen, Fan Zhang, Jia Mi, Zhiqin Gao, Shasha Wang, Qishan Chen, Liying Xing, Bin Wang, Yihai Cao, William C Sessa, Rong Ju, Yizhi Liu, Xuri Li
Ocular neovascularization is a devastating pathology of numerous ocular diseases and is a major cause of blindness. Caveolin-1 (Cav-1) plays important roles in the vascular system. However, little is known regarding its function and mechanisms in ocular neovascularization. Here, using comprehensive model systems and a cell permeable peptide of Cav-1, cavtratin, we show that Cav-1 is a critical player in ocular neovascularization. The genetic deletion of Cav-1 exacerbated and cavtratin administration inhibited choroidal and retinal neovascularization...
September 18, 2017: Proceedings of the National Academy of Sciences of the United States of America
https://www.readbyqxmd.com/read/28923083/prevention-of-c5ar1-signaling-delays-microglial-inflammatory-polarization-favors-clearance-pathways-and-suppresses-cognitive-loss
#13
Michael X Hernandez, Shan Jiang, Tracy A Cole, Shu-Hui Chu, Maria I Fonseca, Melody J Fang, Lindsay A Hohsfield, Maria D Torres, Kim N Green, Rick A Wetsel, Ali Mortazavi, Andrea J Tenner
BACKGROUND: Pharmacologic inhibition of C5aR1, a receptor for the complement activation proinflammatory fragment, C5a, suppressed pathology and cognitive deficits in Alzheimer's disease (AD) mouse models. To validate that the effect of the antagonist was specifically via C5aR1 inhibition, mice lacking C5aR1 were generated and compared in behavior and pathology. In addition, since C5aR1 is primarily expressed on cells of the myeloid lineage, and only to a lesser extent on endothelial cells and neurons in brain, gene expression in microglia isolated from adult brain at multiple ages was compared across all genotypes...
September 18, 2017: Molecular Neurodegeneration
https://www.readbyqxmd.com/read/28921719/inflammation-alters-ampa-stimulated-calcium-responses-in-dorsal-striatal-d2-but-not-d1-spiny-projection-neurons
#14
Carissa D Winland, Nora Welsh, Alberto Sepulveda-Rodriguez, Stefano Vicini, Kathleen A Maguire-Zeiss
Neuroinflammation precedes neuronal loss in striatal neurodegenerative diseases and can be exacerbated by the release of proinflammatory molecules by microglia. These molecules can affect trafficking of AMPARs. The preferential trafficking of calcium-permeable versus impermeable AMPARs can result in disruptions of [Ca(2+) ]i and alter cellular functions. In striatal neurodegenerative diseases, changes in [Ca(2+) ]i and L-type voltage-gated calcium channels (VGCCs) have been reported. Therefore, the present study sought to determine whether a proinflammatory environment alters AMPA-stimulated [Ca(2+) ]i through calcium-permeable AMPARs and/or L-type VGCCs in dopamine-2 and dopamine-1 expressing striatal spiny projection neurons (D2 and D1 SPNs) in the dorsal striatum...
September 16, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28921700/low-dose-fractionated-irradiation-promotes-axonal-regeneration-beyond-reactive-gliosis-and-facilitates-locomotor-function-recovery-after-spinal-cord-injury-in-beagle-dogs
#15
Qiang Zhang, Ying Xiong, Bo Zhu, Bifeng Zhu, Daishi Tian, Wei Wang
Injury to the adult central nervous system (CNS) results in the formation of glial scar tissues. Glial scar-induced failure of regenerative axon pathfinding may limit axon regrowth beyond the lesion site and cause incorrect reinnervation and dystrophic appearance of stalled growth after CNS trauma. Glial scars also upregulate chondroitin sulfate proteoglycans (CSPGs) and expression of proinflammatory factor(s) that form a barrier to axonal regeneration. Therefore, interventions for glial scarring are an attractive strategy for augmenting axonal sprouting and regeneration and overcoming the physical and molecular barriers impeding functional repair...
September 18, 2017: European Journal of Neuroscience
https://www.readbyqxmd.com/read/28918081/developmental-alcohol-exposure-impairs-synaptic-plasticity-without-overtly-altering-microglial-function-in-mouse-visual-cortex
#16
Elissa L Wong, Nina M Lutz, Victoria A Hogan, Cassandra E Lamantia, Helene R McMurray, Jason R Myers, John M Ashton, Ania K Majewska
Fetal alcohol spectrum disorder (FASD), caused by gestational ethanol (EtOH) exposure, is one of the most common causes of non-heritable and life-long mental disability worldwide, with no standard treatment or therapy available. While EtOH exposure can alter the function of both neurons and glia, it is still unclear how EtOH influences brain development to cause deficits in sensory and cognitive processing later in life. Microglia play an important role in shaping synaptic function and plasticity during neural circuit development and have been shown to mount an acute immunological response to EtOH exposure in certain brain regions...
September 13, 2017: Brain, Behavior, and Immunity
https://www.readbyqxmd.com/read/28915816/cramp-deficiency-leads-to-a-pro-inflammatory-phenotype-and-impaired-phagocytosis-after-exposure-to-bacterial-meningitis-pathogens
#17
Eugenia Kress, Julika Merres, Lea-Jessica Albrecht, Sven Hammerschmidt, Thomas Pufe, Simone C Tauber, Lars-Ove Brandenburg
BACKGROUND: Antimicrobial peptides are important components of the host defence with a broad range of functions including direct antimicrobial activity and modulation of inflammation. Lack of cathelin-related antimicrobial peptide (CRAMP) was associated with higher mortality and bacterial burden and impaired neutrophil granulocyte infiltration in a model of pneumococcal meningitis. The present study was designed to characterize the effects of CRAMP deficiency on glial response and phagocytosis after exposure to bacterial stimuli...
September 16, 2017: Cell Communication and Signaling: CCS
https://www.readbyqxmd.com/read/28914133/age-of-donor-of-human-mesenchymal-stem-cells-affects-structural-and-functional-recovery-after-cell-therapy-following-ischaemic-stroke
#18
Susumu Yamaguchi, Nobutaka Horie, Katsuya Satoh, Takeshi Ishikawa, Tsuyoshi Mori, Hajime Maeda, Yuhtaka Fukuda, Shunsuke Ishizaka, Takeshi Hiu, Yoichi Morofuji, Tsuyoshi Izumo, Noriyuki Nishida, Takayuki Matsuo
Cell transplantation therapy offers great potential to improve impairments after stroke. However, the importance of donor age on therapeutic efficacy is unclear. We investigated the regenerative capacity of transplanted cells focusing on donor age (young vs. old) for ischaemic stroke. The quantities of human mesenchymal stem cell (hMSC) secreted brain-derived neurotrophic factor in vitro and of monocyte chemotactic protein-1 at day 7 in vivo were both significantly higher for young hMSC compared with old hMSC...
January 1, 2017: Journal of Cerebral Blood Flow and Metabolism
https://www.readbyqxmd.com/read/28912710/key-aging-associated-alterations-in-primary-microglia-response-to-beta-amyloid-stimulation
#19
Cláudia Caldeira, Carolina Cunha, Ana R Vaz, Ana S Falcão, Andreia Barateiro, Elsa Seixas, Adelaide Fernandes, Dora Brites
Alzheimer's disease (AD) is characterized by a progressive cognitive decline and believed to be driven by the self-aggregation of amyloid-β (Aβ) peptide into oligomers and fibrils that accumulate as senile plaques. It is widely accepted that microglia-mediated inflammation is a significant contributor to disease pathogenesis; however, different microglia phenotypes were identified along AD progression and excessive Aβ production was shown to dysregulate cell function. As so, the contribution of microglia to AD pathogenesis remains to be elucidated...
2017: Frontiers in Aging Neuroscience
https://www.readbyqxmd.com/read/28912686/roles-of-microglial-phagocytosis-and-inflammatory-mediators-in-the-pathophysiology-of-sleep-disorders
#20
REVIEW
Agnes Nadjar, Henna-Kaisa M Wigren, Marie-Eve Tremblay
Sleep serves crucial learning and memory functions in both nervous and immune systems. Microglia are brain immune cells that actively maintain health through their crucial physiological roles exerted across the lifespan, including phagocytosis of cellular debris and orchestration of neuroinflammation. The past decade has witnessed an explosive growth of microglial research. Considering the recent developments in the field of microglia and sleep, we examine their possible impact on various pathological conditions associated with a gain, disruption, or loss of sleep in this focused mini-review...
2017: Frontiers in Cellular Neuroscience
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