LXRs agonists alleviate fat transplantation-induced cognitive dysfunction by inhibiting STING-dependent type I interferon response.

Abstract

Cognitive decline is a comorbidity of neuropathic pain, and is associated with adipose tissue metabolism. We identified that adipose tissue was related to cognitive dysfunction caused by neuropathic pain by constructing adipose tissue transplantation model. We also observed increased expression of dsDNA in mice with cognitive dysfunction, which activated the cGAS-STING pathway, concurrently triggering a type I interferon response and microglial activation. LXRβ also plays a significant role in cognitive dysfunction. LXRβ agonist can ameliorate cognitive dysfunction caused by adipose transplantation by inhibiting the cGAS-STING DNA-sensing pathway. Our findings suggest that LXRβ and the cGAS-STING pathway play key roles in the communication between adipose tissue and the central nervous system, providing novel targets and directions for the treatment of cognitive dysfunction.