Persistent DNA damage alters the neuronal transcriptome suggesting cell cycle dysregulation and altered mitochondrial function

Abstract Oxidative DNA damage induces changes in the neuronal cell cycle and activates a response (DDR) to promote repair, but these processes may be altered under chronic oxidative environment, leading accumulation of unrepaired continued activation DDR. Failure repair can lead apoptosis or senescence, which is characterized by permanent arrest. Increased stress are features brain ageing neurodegeneration, effects persistent neurons not well characterized. We developed model immortalized post‐mitotic vitro exposing them sublethal concentration hydrogen peroxide following ‘double stress’ protocol performed detailed characterization transcriptome using microarray analysis. Persistent significantly expression genes involved regulation, DDR mechanisms, mitochondrial function, suggesting an active replication alterations electron transport chain. Quantitative polymerase chain reaction (qPCR) functional validation experiments confirmed hyperactivation Complex I damage. These further stress, contributing dysfunction ultimately neurodegeneration.