DNA Methylation-Mediated Mfn2 Gene Regulation in the Brain: A Role in Brain Trauma-Induced Mitochondrial Dysfunction and Memory Deficits.

ABSTRACT: Repeated mild traumatic brain injuries (rMTBI) affect mitochondrial homeostasis in the brain. However, mechanisms of long-lasting neurobehavioral effects of rMTBI are largely unknown. Mitofusin 2 (Mfn2) is a critical component of tethering complexes in mitochondria-associated membranes (MAMs) and thereby plays a pivotal role in mitochondrial functions. Herein, we investigated the implications of DNA methylation in the Mfn2 gene regulation, and its consequences on mitochondrial dysfunction in the hippocampus after rMTBI. rMTBI dramatically reduced the mitochondrial mass, which was concomitant with decrease in Mfn2 mRNA and protein levels. DNA hypermethylation at the Mfn2 gene promoter was observed post 30 days of rMTBI. The treatment of 5-Azacytidine, a pan DNA methyltransferase inhibitor,

SUBMITTER: Kulkarni PG 

PROVIDER: S-EPMC11409978 | biostudies-literature | 2023 Oct

REPOSITORIES: biostudies-literature