The molecular pathogenesis of
autism is complex and involves numerous genomic, epigenomic, proteomic, metabolic, and physiological alterations. Elucidating and understanding the molecular processes underlying the pathogenesis of
autism is critical for effective clinical management and prevention of this disorder. The goal of this study is to investigate key molecular alterations postulated to play a role in
autism and their role in the pathophysiology of
autism. In this study we demonstrate that
DNA isolated from the cerebellum of BTBR T+tf/J mice, a relevant mouse model of
autism, and from human post-mortem cerebellum of individuals with
autism, are both characterized by an increased levels of
8-oxo-7-hydrodeoxyguanosine (8-oxodG),
5-methylcytosine (5mC), and
5-hydroxymethylcytosine (5hmC). The increase in
8-oxodG and 5mC content was associated with a markedly reduced expression of the
8-oxoguanine DNA-glycosylase 1 (Ogg1) and increased expression of de novo
DNA methyltransferases 3a and 3b (Dnmt3a and Dnmt3b). Interestingly, a rise in the level of 5hmC occurred without changes in the expression of ten-eleven translocation expression 1 (Tet1) and Tet2 genes, but significantly correlated with the presence of
8-oxodG in
DNA. This finding and similar elevation in
8-oxodG in cerebellum of individuals with
autism and in the BTBR T+tf/J mouse model warrant future large-scale studies to specifically address the role of OGG1 alterations in pathogenesis of
autism.