Sterol dysregulation in Smith-Lemli-Opitz syndrome causes astrocyte immune reactivity through microglia crosstalk.

ABSTRACT: Owing to the need for de novo cholesterol synthesis and cholesterol-enriched structures within the nervous system, cholesterol homeostasis is critical to neurodevelopment. Diseases caused by genetic disruption of cholesterol biosynthesis, such as Smith-Lemli-Opitz syndrome, which is caused by mutations in 7-dehydrocholesterol reductase (DHCR7), frequently result in broad neurological deficits. Although astrocytes regulate multiple neural processes ranging from cell migration to network-level communication, immunological activation of astrocytes is a hallmark pathology in many diseases. However, the impact of DHCR7 on astrocyte function and immune activation remains unknown. We demonstrate that astrocytes from Dhcr7 mutant mice display hallmark signs of reactivity, including increased expre

SUBMITTER: Freel BA 

PROVIDER: S-EPMC10655813 | biostudies-literature | 2022 Dec

REPOSITORIES: biostudies-literature