Microglia Function in the Central Nervous System During Health and Neurodegeneration

Annual Review of Immunology, Journal Year: 2017, Volume and Issue: 35(1), P. 441 - 468

Published: Feb. 22, 2017

Microglia are resident cells of the brain that regulate development, maintenance neuronal networks, and injury repair. serve as macrophages but distinct from other tissue owing to their unique homeostatic phenotype tight regulation by central nervous system (CNS) microenvironment. They responsible for elimination microbes, dead cells, redundant synapses, protein aggregates, particulate soluble antigens may endanger CNS. Furthermore, primary source proinflammatory cytokines, microglia pivotal mediators neuroinflammation can induce or modulate a broad spectrum cellular responses. Alterations in functionality implicated development aging, well neurodegeneration. Recent observations about ontogeny combined with extensive gene expression profiling novel tools study biology have allowed us characterize microglial phenotypes during homeostasis, disease. In this article, we review recent advances our understanding microglia, contribution involvement Moreover, highlight complexity targeting therapeutic intervention neurodegenerative diseases.

Language: Английский

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Sex-Specific Features of Microglia from Adult Mice

Cell Reports, Journal Year: 2018, Volume and Issue: 23(12), P. 3501 - 3511

Published: June 1, 2018

Sex has a role in the incidence and outcome of neurological illnesses, also influencing response to treatments. Neuroinflammation is involved onset progression several diseases, fact that estrogens have anti-inflammatory activity suggests these hormones may be determinant sex-dependent manifestation brain pathologies. We describe significant differences transcriptome adult male female microglia, possibly originating from perinatal exposure sex steroids. Microglia isolated brains maintain sex-specific features when put culture or transplanted opposite sex. Female microglia are neuroprotective because they restrict damage caused by acute focal cerebral ischemia. This study therefore provides insight into distinct perspective on mechanisms underscoring sexual bias susceptibility diseases.

Language: Английский

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Stress, sex hormones, inflammation, and major depressive disorder: Extending Social Signal Transduction Theory of Depression to account for sex differences in mood disorders

Psychopharmacology, Journal Year: 2019, Volume and Issue: 236(10), P. 3063 - 3079

Published: July 29, 2019

Language: Английский

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Gut microbial molecules in behavioural and neurodegenerative conditions

Nature reviews. Neuroscience, Journal Year: 2020, Volume and Issue: 21(12), P. 717 - 731

Published: Oct. 16, 2020

Language: Английский

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Role of Estrogen and Other Sex Hormones in Brain Aging. Neuroprotection and DNA Repair

Frontiers in Aging Neuroscience, Journal Year: 2017, Volume and Issue: 9

Published: Dec. 22, 2017

Aging is an inevitable biological process characterized by a progressive decline in physiological function and increased susceptibility to disease. The detrimental effects of aging are observed all tissues, the brain being most important one due its main role homeostasis organism. As our knowledge about underlying mechanisms increases, potential approaches preserve rise significantly. Accumulating evidence suggests that loss genomic maintenance may contribute aging, especially central nervous system owing low DNA repair capacity. Sex hormones, particularly estrogens, possess potent antioxidant properties play roles maintaining normal reproductive non-reproductive functions. They exert neuroprotective actions their during natural or surgical menopause associated with mitochondrial dysfunction, neuroinflammation, synaptic decline, cognitive impairment risk age-related disorders. Moreover, sex hormones has been suggested promote accelerated phenotype eventually leading development hypometabolism, feature often menopausal women prodromal Alzheimer’s Although data on relation between still limited, various investigations have linked hormone levels different enzymes. Here, we review estrogen anti-aging mechanisms, which currently area intense study, together effect they capacity

Language: Английский

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Sex differences and the neurobiology of affective disorders

Neuropsychopharmacology, Journal Year: 2018, Volume and Issue: 44(1), P. 111 - 128

Published: July 9, 2018

Language: Английский

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Microglia morphophysiological diversity and its implications for the CNS

Frontiers in Immunology, Journal Year: 2022, Volume and Issue: 13

Published: Oct. 19, 2022

Microglia are mononuclear phagocytes of mesodermal origin that migrate to the central nervous system (CNS) during early stages embryonic development. After colonizing CNS, they proliferate and remain able self-renew throughout life, maintaining number microglia around 5-12% cells in CNS parenchyma. They considered play key roles development, homeostasis innate immunity CNS. exceptionally diverse their morphological characteristics, actively modifying shape processes soma response different stimuli. This broad spectrum responses is be closely correlated range functions health disease. However, morphophysiological attributes microglia, structural functional features microglia-neuron interactions, largely unknown. Here, we assess current knowledge microglial morphologies, with a focus on correlation between function. We also outline some challenges, opportunities, future directions will help us tackle unanswered questions about continue unravelling mysteries all its shapes.

Language: Английский

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Interplay of gut microbiota and oxidative stress: Perspective on neurodegeneration and neuroprotection

Journal of Advanced Research, Journal Year: 2021, Volume and Issue: 38, P. 223 - 244

Published: Sept. 17, 2021

Recent research on the implications of gut microbiota brain functions has helped to gather important information relationship between them. Pathogenesis neurological disorders is found be associated with dysregulation gut-brain axis. Some bacteria metabolites are directly increase in reactive oxygen species levels, one most risk factors neurodegeneration. Besides their morbid association, also play a significant role reducing onset these life-threatening disorders.Studies done recent past raises two link and brain: "gut microbiota-oxidative stress-neurodegeneration" microbiota-antioxidant-neuroprotection. This review aims gives deep insight our readers, collective studies done, focusing mediated oxidative stress involved neurodegeneration along focus those showing involvement neuroprotection.This focused three main key concepts. Firstly, mounting evidences from clinical preclinical arenas shows influence resulting dysfunctional processes. Therefore, we describe potential influencing vulnerability stress, budding causative Alzheimer's Parkinson's disease. Secondly, contributing roles been observed attenuating inflammation via its own or by producing secondary and, modulation population antioxidative anti-inflammatory probiotics have shown promising neuro resilience. Thirdly, high throughput silico tools databases correlation microbiome, health, thus providing fascinating perspective new avenues for therapeutic options.

Language: Английский

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Neurosteroids as regulators of neuroinflammation

Frontiers in Neuroendocrinology, Journal Year: 2019, Volume and Issue: 55, P. 100788 - 100788

Published: Sept. 9, 2019

Neuroinflammation is a physiological protective response in the context of infection and injury. However, neuroinflammation, especially if chronic, may also drive neurodegeneration. Neurodegenerative diseases, such as multiple sclerosis (MS), Alzheimer's disease (AD), Parkinson's (PD) traumatic brain injury (TBI), display inflammatory activation microglia astrocytes. Intriguingly, central nervous system (CNS) highly steroidogenic environment synthesizing steroids de novo, well metabolizing deriving from circulation. Neurosteroid synthesis can be substantially affected by while, turn, several steroids, 17β-estradiol, dehydroepiandrosterone (DHEA) allopregnanolone, regulate neuroinflammatory responses. Here, we review role neurosteroids neuroinflammation MS, AD, PD TBI describe underlying molecular mechanisms. Moreover, introduce concept that synthetic neurosteroid analogues could potentially utilized for treatment neurodegenerative diseases future.

Language: Английский

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Neuroprotection by dihydrotestosterone in LPS-induced neuroinflammation

Neurobiology of Disease, Journal Year: 2020, Volume and Issue: 140, P. 104814 - 104814

Published: Feb. 19, 2020

Microglia-induced neuroinflammation plays a vital role in the etiology and progression of neurodegenerative diseases, including Alzheimer's disease, Parkinson's disease multiple sclerosis. The neuroprotective androgens, testosterone its metabolite dihydrotestosterone (DHT), has been increasingly demonstrated these but few studies investigated effects androgen on neuroinflammation. This study DHT lipopolysaccharide (LPS)-induced neuroinflammation, neuronal damage behavioral dysfunction, as well underlying mechanisms. We showed that inhibited LPS-induced release proinflammatory factors, TNF-α, IL-1β, IL-6; iNOS, COX-2, NO, PGE2 BV2 cells primary microglia by suppressing TLR4-mediated NF-κB MAPK p38 signaling pathways, thus protecting SH-SY5Y neurons from inflammatory induced activated microglia. In an mouse model, endogenous depletion castration exacerbated responses upregulating levels IL-6, COX-2 serum brain increasing LR4-mediated pathway activation, were restored exogenous supplementation. Moreover, also regulated mRNA anti-inflammatory cytokines IL-10 IL-13 brain. addition, modulated expression Aβ, apoptotic proteins caspase-3, Bcl-2, Bax, synaptophysin, LPS-treated brains. Further tests revealed ameliorated spatial learning impairment motor incoordination, partly improved locomotor activity LPS-injected mice. Therefore, this suggests exerts anti-neuroinflammatory effects; thus, replacement therapy is potential therapeutic strategy for improving cognitive function neuroinflammation-related diseases.

Language: Английский

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