100 - Mechanism of Neuroprotection by Capsaicin in a Model of Parkinson's Disease

Abstract

Parkinson’s disease (PD) is characterised by progressive loss of motor function and dopaminergic neuron (DN) density. The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) is neurotoxic to DN in the mouse substantia nigra yielding PD-like symptoms. Red peppers contain capsaicin that can protect neurons in an in vitro model of acute oxidative insult (Fong and Witting unpublished). We aim to test whether capsaicin prevents neuronal loss and brain function in a mouse model of PD. Male C57BL/6 mice were pre-treated with vehicle or capsaicin (1 mg/kg) prior to saline or MPTP (25 mg/kg/day) treatment over 2 consecutive days. Gait was assessed on a subset of mice six days after the onset of treatment. Serum and various organs were harvested for biochemical and histological analyses. MPTP-treated mice displayed signs of akinesia and increased number of abnormal steps; this was restored to normal with capsaicin pre-treatment. Total DN counts decreased in the MPTP-treated animals while capsaicin pre-treatment improved viability. Cerebral levels of IL-6, TNF-α and IFN-γ remained unchanged. MPTP treatment increased SOD and decreased catalase activity while capsaicin pre-treatment restored SOD and catalase activity to control levels. The dose of MPTP employed did not significantly alter gait dynamics but as anticipated did induce noticeable decline in DN density. Capsaicin pre-treatment protected DN from MPTP, possibly via an augmented antioxidant system.