Microglial brain region− dependent diversity and selective regional sensitivities to aging

K Grabert, T Michoel, MH Karavolos, S Clohisey… - Nature …, 2016 - nature.com
K Grabert, T Michoel, MH Karavolos, S Clohisey, JK Baillie, MP Stevens, TC Freeman
Nature neuroscience, 2016nature.com
Microglia have critical roles in neural development, homeostasis and neuroinflammation
and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration
often occurs in disease-specific, spatially restricted patterns, the origins of which are
unknown. We performed to our knowledge the first genome-wide analysis of microglia from
discrete brain regions across the adult lifespan of the mouse, and found that microglia have
distinct region-dependent transcriptional identities and age in a regionally variable manner …
Abstract
Microglia have critical roles in neural development, homeostasis and neuroinflammation and are increasingly implicated in age-related neurological dysfunction. Neurodegeneration often occurs in disease-specific, spatially restricted patterns, the origins of which are unknown. We performed to our knowledge the first genome-wide analysis of microglia from discrete brain regions across the adult lifespan of the mouse, and found that microglia have distinct region-dependent transcriptional identities and age in a regionally variable manner. In the young adult brain, differences in bioenergetic and immunoregulatory pathways were the major sources of heterogeneity and suggested that cerebellar and hippocampal microglia exist in a more immune-vigilant state. Immune function correlated with regional transcriptional patterns. Augmentation of the distinct cerebellar immunophenotype and a contrasting loss in distinction of the hippocampal phenotype among forebrain regions were key features during aging. Microglial diversity may enable regionally localized homeostatic functions but could also underlie region-specific sensitivities to microglial dysregulation and involvement in age-related neurodegeneration.
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