Microglia emerge as central players in brain disease

Nature Medicine, Journal Year: 2017, Volume and Issue: 23(9), P. 1018 - 1027

Published: Sept. 1, 2017

Language: Английский

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Microglia and Beyond: Innate Immune Cells As Regulators of Brain Development and Behavioral Function

Frontiers in Immunology, Journal Year: 2018, Volume and Issue: 9

Published: April 13, 2018

Innate immune cells play a well-documented role in the etiology and disease course of many brain-based conditions, including multiple sclerosis, Alzheimer's disease, traumatic brain spinal cord injury, cancers. In contrast, it is only recently becoming clear that innate cells, primarily resident macrophages called microglia, are also key regulators development. This review summarizes current state knowledge regarding microglia development, with particularly emphasis on how during development distinct from later life. We summarize effects early life perturbations function developing brain, biological sex plays function, potential may developmental disorders. Finally, given new field neuroimmunology is, we highlight what has yet to be learned about shape behavior.

Language: Английский

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Beyond infection - Maternal immune activation by environmental factors, microglial development, and relevance for autism spectrum disorders

Experimental Neurology, Journal Year: 2017, Volume and Issue: 299, P. 241 - 251

Published: July 8, 2017

Language: Английский

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Microglia and the Brain: Complementary Partners in Development and Disease

Annual Review of Cell and Developmental Biology, Journal Year: 2018, Volume and Issue: 34(1), P. 523 - 544

Published: Aug. 8, 2018

An explosion of findings driven by powerful new technologies has expanded our understanding microglia, the resident immune cells central nervous system (CNS). This wave discoveries fueled a growing interest in roles that these play development CNS and neuropathology diverse array disorders. In this review, we discuss crucial microglia shaping brain—from their influence on neurons glia within developing to synaptic maturation brain wiring—as well as some obstacles overcome when assessing contributions normal development. Furthermore, examine how developmental functions are perturbed or remerge neurodevelopmental neurodegenerative disease.

Language: Английский

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Innate immunity at the crossroads of healthy brain maturation and neurodevelopmental disorders

Nature reviews. Immunology, Journal Year: 2021, Volume and Issue: 21(7), P. 454 - 468

Published: Jan. 21, 2021

Language: Английский

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The Inflamed Brain in Schizophrenia: The Convergence of Genetic and Environmental Risk Factors That Lead to Uncontrolled Neuroinflammation

Frontiers in Cellular Neuroscience, Journal Year: 2020, Volume and Issue: 14

Published: Aug. 27, 2020

Schizophrenia is a disorder with heterogeneous etiology involving complex interplay between genetic and environmental risk factors. The immune system now known to play vital roles in nervous function pathology through regulating neuronal glial development, synaptic plasticity, behavior. In this regard, the positioned as common link seemingly diverse factors for schizophrenia. Synthesizing information about how immune-brain axis affected by multiple these might interact schizophrenia necessary better understand pathogenesis of disease. Such knowledge will aid development more translatable animal models that may lead effective therapeutic interventions. Here, we provide an overview modulate function. We also explore including exposure pollution, gut dysbiosis, maternal activation early-life stress, consequences are linked microglial dysfunction. propose morphological signaling deficits blood-brain barrier, observed some individuals schizophrenia, can act gateway peripheral central inflammation, thus affecting microglia their essential functions. Finally, describe response neuroinflammation impact on brain homeostasis, well pathophysiology.

Language: Английский

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Understanding the Role of the Gut Microbiome in Brain Development and Its Association With Neurodevelopmental Psychiatric Disorders

Frontiers in Cell and Developmental Biology, Journal Year: 2022, Volume and Issue: 10

Published: April 14, 2022

The gut microbiome has a tremendous influence on human physiology, including the nervous system. During fetal development, initial colonization of coincides with development system in timely, coordinated manner. Emerging studies suggest an active involvement and its metabolic by-products regulating early brain development. However, any disruption during this developmental process can negatively impact functionality, leading to range neurodevelopment neuropsychiatric disorders (NPD). In review, we summarize recent evidence as how association major neurodevelopmental psychiatric such autism spectrum disorders, attention-deficit hyperactivity disorder, schizophrenia. Further, discuss alterations also play role inducing drug resistance affected individuals. We propose model that establishes direct link dysbiosis exacerbated inflammatory state, functional deficits associated NPD. Based existing research, framework whereby diet intervention boost mental wellness subjects call for further research better understanding mechanisms govern gut-brain axis may lead novel approaches study pathophysiology treatment disorders.

Language: Английский

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Microglial morphometric analysis: so many options, so little consistency

Frontiers in Neuroinformatics, Journal Year: 2023, Volume and Issue: 17

Published: Aug. 10, 2023

Quantification of microglial activation through morphometric analysis has long been a staple the neuroimmunologist’s toolkit. Microglial morphological phenomics can be conducted either manual classification or constructing digital skeleton and extracting data from it. Multiple open-access paid software packages are available to generate these skeletons via semi-automated and/or fully automated methods with varying degrees accuracy. Despite advancements in morphometrics (quantitative measures cellular morphology), there limited development tools analyze datasets they generate, particular those containing parameters tens thousands cells analyzed by pipelines. In this review, we compare critique approaches using cluster machine learning driven predictive algorithms that have developed tackle large datasets, propose improvements for methods. particular, highlight need commitment open science groups developing classifiers. Furthermore, call attention communication between strong engineering/computer background neuroimmunologists produce effective analytical simplified operability if see their wide-spread adoption glia biology community.

Language: Английский

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Microglia as Dynamic Cellular Mediators of Brain Function

Trends in Molecular Medicine, Journal Year: 2019, Volume and Issue: 25(11), P. 967 - 979

Published: Oct. 6, 2019

Language: Английский

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Prenatal Immune Challenge in Mice Leads to Partly Sex-Dependent Behavioral, Microglial, and Molecular Abnormalities Associated with Schizophrenia

Frontiers in Molecular Neuroscience, Journal Year: 2018, Volume and Issue: 11

Published: Feb. 8, 2018

Epidemiological studies revealed that environmental factors comprising prenatal infection are strongly linked to risk for later development of neuropsychiatric disorders such as schizophrenia. Considering strong sex differences in schizophrenia and its increased prevalence males, we designed a methodological approach investigate possible pathophysiological mechanisms. Prenatal immune challenge was modeled by systemic administration the viral mimic polyinosinic-polycytidylic acid (Poly I:C) C57BL/6 mice at embryonic day 9.5. The consequences on behavior, gene expression, microglia-brain cells critical normal development-were characterized male vs. female offspring adulthood. cerebral cortex, hippocampus, cerebellum, regions where structural functional alterations were mainly described patients, selected cellular molecular analyses. Confocal electron microscopy most pronounced microglial distribution, arborization, stress, synaptic interactions hippocampus exposed Poly I:C. Sex microglia also measured under both steady-state I:C conditions. These accompanied behavioral impairment, affecting instance sensorimotor gating, males. Consistent with these results, expression genes related inflammation cortex males challenged Overall, findings suggest schizophrenia's higher incidence might be associated, among other mechanisms, an reactivity challenges, hence determining disease outcomes into

Language: Английский

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