Introduction and hypothesisThe degeneration and lost on dopaminergic neurons in midbrain may cause Parkinson's disease, and it is one of the most common neurodegenerative disease in human. Rotenone is a natural lipophilic toxic compound that is easy to cross the blood‐brain barrier, and widely used as insecticide and pesticide. Rotenone may impair mitochondrial oxidative phosphorylation and lead to dopaminergic neuron loss. In this study we investigated the protective effects of caffeine on rotenone‐induced Parkinson's disease models in vitro and in vivo.MethodsIn vitro, the dopaminergic cell line, SH‐SY5Y cells, is pretreated with caffeine (0~100 mM) for 30 mins and followed by treatment with rotenone (0~10 mM) for 1 hr~24 hr respectively. The cell survival rate, proliferation and morphology were analysis by flow cytometry, ELISA, Cell Counting Kit‐8(CCK‐8) and histology studies. Cell apoptosis/necrosis were analyzed by Annexin‐V/PI staining using flow cytometry. In vivo, the SD rats pretreated with caffeine (10 mg/kg daily, P.O.) or saline and followed treated with rotenone (1 mg/kg daily for 1 week, S.C.). The expressions of apoptosis and autophagy related proteins were analyzed by western blotting. The locomotion of rats were carried out by open field tests.ResultsCaffeine treatments (0–100 mM) had rarely toxic effect on SH‐SY5Y cell lines but could promote autophagy. The SH‐SY5Y cells treated with 1 nM rotenone for 8 hr may decrease the mitochondrial activity of around 60%. Pretreated with caffeine (>2 mM) for 30 min and followed treated with 10 nM rotenone for 8 hr could significantly increase total cell numbers and decrease the cell apoptotic ratio, but no effect on the necrosis ratio and did not restore the mitochondrial activity on rotenone‐induced dopaminergic cell toxicity. The locomotion of SD rats that pretreated with caffeine was better than the saline control in rotenone‐induced Parkinson's disease model. After exposure to rotenone, the situation of recovery by bradykinesia in daily caffeine‐treated group is more obviously than saline control.ConclusionsIn rotenone‐induced Parkinson's disease model, caffeine could facilitate autophagy, increase cell viability and animal locomotion. Our results indicated that caffeine has the potential protective effects on rotenone‐induced Parkinson's disease model.Support or Funding InformationKMU‐TP105E37This abstract is from the Experimental Biology 2018 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.