Sex-Specific Features of Microglia from Adult Mice

Summary

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

Graphical Abstract

Highlights

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  Transcriptome sequencing indicates sexual differentiation in adult murine microglia

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  Female microglia show a neuroprotective phenotype, independent from hormonal cues

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  Female microglia phenotype is retained after transfer into male brains

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  The presence of female microglia protects male brains from ischemic stroke

Abstract

Villa et al. find significant differences in the transcriptomes of microglia isolated from the brains of healthy adult male and female mice. They find that microglia from female mice are neuroprotective and that they retain this functional ability when transferred into the brains of male mice.