Astrocytic IGF-1 and IGF-1R Orchestrate Mitophagy in Traumatic Brain Injury via Exosomal miR-let-7e.

ABSTRACT: Defective brain hormonal signaling and autophagy have been associated with neurodegeneration after brain insults, characterized by neuronal loss and cognitive dysfunction. However, few studies have linked them in the context of brain injury. Insulin-like growth factor-1 (IGF-1) is an important hormone that contributes to growth, cell proliferation, and autophagy and is also expressed in the brain. Here, we assessed the clinical data from TBI patients and performed both in vitro and in vivo experiments with proteomic and gene-chip analysis to assess the functions of IGF-1 in mitophagy following TBI. We show that reduced plasma IGF-1 is correlated with cognition in TBI patients. Overexpression of astrocytic IGF-1 improves cognitive dysfunction and mitophagy in TBI mice. Mechanically, proteom

SUBMITTER: Dabin R 

PROVIDER: S-EPMC9433209 | biostudies-literature | 2022

REPOSITORIES: biostudies-literature