CircRNA Itm2b induces oxidative stress via the interaction with Sirt1-Nox4 to aggravate sleep disturbances after traumatic brain injury.

Abstract

Sleep disorders (SD) are common sequelae following traumatic brain injury (TBI) and may be linked to mitochondrial oxidative stress dysregulation after TBI. Increasing evidence showed that circRNAs play crucial roles in nervous system diseases. However, the involvement of circRNAs in sleep disturbances after TBI is not characterized. In this study, differentially expressed circRNAs were identified by RNA sequencing. Sleep quality in TBI patients was assessed through sleep scales and electroencephalograms. Further experiments were conducted to investigate the role of circItm2b. We found that circItm2b was elevated and involved sleep disorder in TBI patients. Over-expression of circItm2b might aggravate sleep disturbances in mice after TBI. Mechanically, circItm2b regulates Nox4 expression through binding Sirt1, which influences mitochondrial oxidative stress-caused circadian protein losses. Moreover, the knockdown of circItm2b attenuated mitochondrial oxidative stress-induced circadian proteins losses via circItm2b/Sirt1/Nox4 axis after TBI, which might suggest that circItm2b may serve as a prognostic marker for improving sleep disorders and represent a promising therapeutic target for TBI-related sleep disturbances.