Abstract
INTRODUCTION: Parkinson's disease (PD) is the second most common neurodegenerative disorder, without any widely available curative therapy. Metabolomics is a powerful tool which can be used to identify unexpected pathway-related disease progression and pathophysiological mechanisms. In this study, metabolomics in brain, plasma and liver was investigated in an experimental PD model, to discover small molecules that are associated with dopaminergic cell loss. METHODS: Sprague Dawley (SD) rats were injected unilaterally with 6-hydroxydopamine (6-OHDA) or saline for the vehicle control group into the medial forebrain bundle (MFB) to induce loss of dopaminergic neurons in the substantia nigra pars compacta. Plasma, midbrain and liver samples were collected for metabolic profiling. Multivariate and univariate analyses revealed metabolites that were altered in the PD group. RESULTS: In plasma, palmitic acid (q = 3.72 × 10(-2), FC = 1.81) and stearic acid (q = 3.84 × 10(-2), FC = 2.15), were found to be increased in the PD group. Palmitic acid (q = 3.5 × 10(-2)) and stearic acid (q = 2.7 × 10(-2)) correlated with test scores indicative of motor dysfunction. Monopalmitin (q = 4.8 × 10(-2), FC = -11.7), monostearin (q = 3.72 × 10(-2), FC = -15.1) and myo-inositol (q = 3.81 × 10(-2), FC = -3.32), were reduced in the midbrain. The liver did not have altered levels of these molecules. CONCLUSION: Our results show that saturated free fatty acids, their monoglycerides and myo-inositol metabolism in the midbrain and enteric circulation are associated with 6-OHDA-induced PD pathology.