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- W2891428842 abstract "Abstract Astrogliosis is a hallmark of neuroinflammatory disorders such as multiple sclerosis (MS). A detailed understanding of the underlying molecular mechanisms governing astrogliosis might facilitate the development of therapeutic targets. We investigated whether Nav1.5 expression in astrocytes plays a role in the pathogenesis of experimental autoimmune encephalomyelitis (EAE), a murine model of MS. We created a conditional knockout of Nav1.5 in astrocytes and determined whether this affects the clinical course of EAE, focal macrophage and T cell infiltration, and diffuse activation of astrocytes. We show that deletion of Nav1.5 from astrocytes leads to significantly worsened clinical outcomes in EAE, with increased inflammatory infiltrate in both early and late stages of disease, unexpectedly, in a sex‐specific manner. Removal of Nav1.5 in astrocytes leads to increased inflammation in female mice with EAE, including increased astroglial response and infiltration of T cells and phagocytic monocytes. These cellular changes are consistent with more severe EAE clinical scores. Additionally, we found evidence suggesting possible dysregulation of the immune response—particularly with regard to infiltrating macrophages and activated microglia—in female Nav1.5 KO mice compared with WT littermate controls. Together, our results show that deletion of Nav1.5 from astrocytes leads to significantly worsened clinical outcomes in EAE, with increased inflammatory infiltrate in both early and late stages of disease, in a sex‐specific manner." @default.
- W2891428842 created "2018-09-27" @default.
- W2891428842 creator A5002957653 @default.
- W2891428842 creator A5017275999 @default.
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- W2891428842 creator A5062250759 @default.
- W2891428842 creator A5063532180 @default.
- W2891428842 creator A5072867035 @default.
- W2891428842 date "2018-09-08" @default.
- W2891428842 modified "2023-09-26" @default.
- W2891428842 title "Nav1.5 in astrocytes plays a sex-specific role in clinical outcomes in a mouse model of multiple sclerosis" @default.
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