Neuroprotective effect of 17-beta estradiol against 1-methyl-4-phenylpyridium induced dopaminergic neuronal toxicity in vitro

Abstract

Parkinson's disease is an idiopathic disease characterized by loss of dopaminergic neurons in the basal ganglia. It has been suggested that estrogen possesses neuroprotective effects in neurodegenerative disorders. In this study, primary mesencephalic cultures were prepared from embryonic (day 14) rat. Five different concentrations (0.1 muM-10 muM) of 17-beta estradiol were tested. 17-beta estradiol and 1-methyl-4-phenylpyridinium (MPP+) (10 muM) were co-administered to the culture on the second day in vitro (DIV 2), and were withdrawn after 48 hours. Cultures were harvested on DIV 6. Dopaminergic neurons in the cultures were visualized by tyrosine hydroxylase (TH) immunocytochemistry. The number of TH-positive neurons was counted under phase-contrast microscope. 48.2% of neurons in the control culture were found to be TH-positive. 10 muM MPP+ reduced the percentage of TH-positive neurons to 24.04% (p<0.001). Co-administration of MPP+ and 17-beta estradiol with concentrations higher than 1 muM, which peak at 5 muM, shown significant increase in the percentage of TH-positive neurons. (1 muM: 37.19%, p<0.01; 5 muM: 38.20%, p<0.001; 10 muM: 33.97%, p<0.05). The result suggests that 17-beta estradiol may play a neuroprotective role against MPP+ induced dopaminergic toxicity.