Role of SIRT1/PGC-1α in mitochondrial oxidative stress in autistic spectrum disorder

Autistic spectrum disorder (ASD) is a neurodevelopmental disorder and has a high prevalence in children. Recently, mitochondrial oxidative stress has been proposed to be associated with ASD. Besides, SIRT1/PGC-1 alpha signaling plays an important role in combating oxidative stress. In this study, we sought to determine the role of SIRT1/PGC-1 alpha signaling in the ASD lymphoblastoid cell lines (LCLs). In this study, the mRNA and protein expressions of SIRT1/PGC-1 alpha axis genes were assessed in 35 children with ASD and 35 healthy controls (matched for age, gender, and IQ). An immortalized LCL was established by transforming lymphocytes with Epstein-Barr virus. Next, we used ASD LCLs and control LCLs to detect SIRT1/PGC-1 alpha axis genes expression and oxidative damage. Finally, the effect of overexpression of PGC-1 alpha on oxidative injury in the ASD LCLs was determined. SIRT1/PGC-1 alpha axis genes expression was downregulated at RNA and protein levels in ASD patients and LCLs. Besides, the translocation of cytochrome c and DIABLO from mitochondria to the cytosol was found in the ASD LCLs. Moreover, the intracellular reactive oxygen species (ROS) and mitochondrial ROS and cell apoptosis were increased in the ASD LCLs. However, overexpression of PGC-1 alpha upregulated the SIRT1/PGC-1 alpha axis genes expression and reduced cytochrome c and DIABLO release in the ASD LCLs. Also, overexpression of PGC-1 alpha reduced the ROS generation and cell apoptosis in the ASD LCLs. Overexpression of PGC-1 alpha could reduce the oxidative injury in the ASD LCLs, and PGC-1 alpha may act as a target for treatment.