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Understanding Microglial Diversity and Implications for Neuronal Function in Health and Disease

De Schepper, S; Crowley, G; Hong, S; (2021) Understanding Microglial Diversity and Implications for Neuronal Function in Health and Disease. Developmental Neurobiology , 81 (5) pp. 507-523. 10.1002/dneu.22777. Green open access

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Abstract

Genetic data implicate microglia as central players in brain health and disease, urging the need to better understand what microglia do in the brain. Microglia are critical partners in neuronal wiring and function during development and disease. Emerging literature suggests that microglia have diverse functional roles, raising the intriguing question of which functions of microglia become impaired in disease to undermine proper neuronal function. It is also becoming increasingly clear that microglia exist in heterogeneous cell states. Microglial cell states appear context-dependent, i.e., age, sex, location and health of their microenvironment; these are further influenced by external signaling factors including gut microbiota and lipid metabolites. These data altogether suggest that microglia exist in functional clusters that impact, and are impacted by, surrounding neuronal microenvironment. However, we still lack understanding of how we can translate microglia cell states into function. Here, we summarize the state-of-the-art on microglial diverse functions in relation to neuronal health. Then we discuss heterogeneity during developing, healthy adult and diseased brains, and whether this may be pre-determined by origin and/or regulated by local milieu. Finally, we propose that it is critical to gain high-resolution functional discernment into microglia-neuron interactions while preserving the spatial architecture of the tissue. Such insight will reveal specific targets for biomarker and therapeutic development toward microglia-neuron crosstalk in disease.

Type: Article
Title: Understanding Microglial Diversity and Implications for Neuronal Function in Health and Disease
Location: United States
Open access status: An open access version is available from UCL Discovery
DOI: 10.1002/dneu.22777
Publisher version: http://dx.doi.org/10.1002/dneu.22777
Language: English
Additional information: © 2020 The Authors. Developmental Neurobiology published by Wiley Periodicals LLC. This is an open access article under the terms of the Creative Commons Attribution License, which permits use, distribution and reproduction in any medium, provided the original work is properly cited.
Keywords: Alzheimer’s Disease, Microglia, Neuro-Immune Crosstalk, Synapse, Transcriptional Heterogeneity
UCL classification: UCL
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology
UCL > Provost and Vice Provost Offices > School of Life and Medical Sciences > Faculty of Brain Sciences > UCL Queen Square Institute of Neurology > UK Dementia Research Institute
URI: https://discovery.ucl.ac.uk/id/eprint/10107690
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