Application of OpenArray Technology to Assess Changes in the Expression of Functionally Significant Genes in the Substantia Nigra of Mice in a Model of Parkinson's Disease.

Abstract

Studying the molecular mechanisms of the pathogenesis of Parkinson's disease (PD) is critical to improve PD treatment. We used OpenArray technology to assess gene expression in the substantia nigra (SN) cells of mice in a 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) model of PD and in controls. Among the 11 housekeeping genes tested, Rps27a was taken as the reference gene due to its most stable expression in normal and experimental conditions. From 101 genes encoding functionally significant proteins of nigrostriatal dopaminergic neurons, 57 highly expressed genes were selected to assess their expressions in the PD model and in the controls. The expressions of Th, Ddc, Maoa, Comt, Slc6a3, Slc18a2, Drd2, and Nr4a2 decreased in the experiment compared to the control, indicating decreases in the synthesis, degradation, and transport of dopamine and the impaired autoregulation of dopaminergic neurons. The expressions of Tubb3, Map2, Syn1, Syt1, Rab7, Sod1, Cib1, Gpx1, Psmd4, Ubb, Usp47, and Ctsb genes were also decreased in the MPTP-treated mice, indicating impairments of axonal and vesicular transport and abnormal functioning of the antioxidant and ubiquitin-proteasome systems in the SN. The detected decreases in the expressions of Snca, Nsf, Dnm1l, and Keap1 may serve to reduce pathological protein aggregation, increase dopamine release in the striatum, prevent mitophagy, and restore the redox status of SN cells.