Altered DNA repair related proteins in Parkinson’s disease model VMAT2 Lo mice

Abstract

Abstract DNA damage and repair processes play an important role in the pathogenesis of age-related neurodegenerative diseases such as Parkinson’s Disease (PD), as DNA repair pathways delay cell senescence and aging by maintaining genomic integrity. In the present study, the expression of DNA repair-related enzymes and proteins were examined in the brain of VMAT2 Lo mice, a PD animal model. The results demonstrated that in the frontal cortex (FC) and locus coeruleus (LC) of VMAT2 Lo mice at 2, 6, and 15 months of age, OGG1 protein levels were significantly increased. However, OGG1 protein levels in the hippocampus, substantia nigra (SN) and LC of these model mice at 18 and 23 months of age exhibited a marked reduction. This reduction of OGG1 proteins in the hippocampus and SN was accompanied by the relatively similar diminishment of their mRNAs. Furthermore, immunochemical and immunofluorescence staining demonstrated that in most measured brain regions, the immunoreactivities of PARP1, ERCC1, XRCC1 and PCNA, four enzymes and protein related to DNA repair processes, were considerably reduced in VMAT2 Lo mice at 18 and 23 months of age. These analysis results reveal the DNA oxidative damage triggers the activation of DNA repair process in this PD model, and provides important insights for the involvement of DNA repair processes in the PD pathogenesis.