Transcriptomics

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Early Modulation of the Gut Microbiome by Female Sex Hormones Alters Amyloid Pathology and Microglial Function


ABSTRACT: It is well-established that women are disproportionately affected by Alzheimer’s disease (AD). The mechanisms underlying this sex-specific disparity are not fully understood, but several factors that are often associated-including interactions of sex hormones, genetic factors, and the gut microbiome-likely contribute to the disease's etiology. Here, we have examined the role of sex hormones and the gut microbiome in mediating A amyloidosis and neuroinflammation in APPPS1-21 mice. We report that postnatal gut microbiome perturbation in female APPPS1-21 mice leads to an elevation in levels of circulating estradiol. Early stage ovariectomy (OVX) leads to a reduction of plasma estradiol that is correlated with a significant alteration of gut microbiome composition and reduction in A pathology. On the other hand, supplementation of OVX-treated animals with estradiol restores A burden and influences gut microbiome composition. The reduction of A pathology with OVX is paralleled by diminished levels of plaque-associated MGnD-type microglia while estradiol supplementation of OVX-treated animals leads to a restoration of activated microglia around plaques. In summary, our investigation elucidates the complex interplay between sex-specific hormonal modulations, gut microbiome dynamics, metabolic perturbations, and microglial functionality in the pathogenesis of Alzheimer's disease.

ORGANISM(S): Mus musculus

PROVIDER: GSE245831 | GEO | 2024/02/08

REPOSITORIES: GEO

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