EVIDENCE OF EARLY CEREBELLAR DYSFUNCTION IN PRESYMPTOMATIC PARKINSON’S DISEASE:DATA FROM MRI AND BIOCHEMICAL ANALYSIS

POSTER PRESENTATIONS

Objective. With the hope of identifying early biomarkers prior to any signs of PD we investigated the PINK1 (PTENinduced putative kinase 1) knock-out (KO) rat. Background. Genetic models of Parkinson’s disease (PD) that recapitulate many of the neurobiological and behavioral aspects of disease progression are highly desired as we look to identify early biomarkers of PD long before the symptomology. PINK1 is a mitochondrial protein kinase involved in protecting neurons from stress-induced mitochondrial dysfunction. Mutation in the PINK1 gene is a leading risk factor in familial PD. Methods. 3D segmented and annotated MRI rat atlas with quantitative anisotropy to identify sites of gray matter injury from 171 brain areas in wild type (WT) and PINK1 KO. Results. Cerebellum and the deep cerebellar nuclei as a potential areas vulnerable to change in early Parkinson’s, along with elevated oxidative stress. Immunohistochemical analysis confirmed these results. Mitochondrial dysfunction was also identified in the cerebellum and the deep cerebral nuclei. Consistent with the previous results, cerebellum showed significant changes in ATP levels, GSH levels, oxidative damage and DNA methylation levels. These changes in cerebellum and cerebellar nuclei were more pronounced as compared to the SN / VTA. Conclusion. Dysfunction in Cerebellum and deep cerebral nuclei could be used as an early biomarker for identification of PD Grants. Michael J Fox Foundation, SAGE Labs.