Effects and potential mechanisms of rapamycin on MPTP-induced acute Parkinson’s disease in mice

Abstract

BACKGROUND: Parkinson's disease is the second major neurodegenerative diseases secondarily to Alzheimer's disease. Rapamycin is a fermentation product, which derived from Streptomyces hygroscopius. The aim of this study is to investigate the effect of rapamycin and its potential mechanisms on the acute attack of 1-methyl-4-phenyl-1,2,3,6-four hydrogen pyridine (MPTP) induced Parkinson's disease (PD) in mice. METHODS: PD model was established by intraperitoneal injection of MPTP for 5 days. The effect of intraperitoneal injection of rapamycin for treating the symptoms caused by PD was evaluated by behavior observation and HE pathological section. In order to understand the possible mechanism, immunofluorescence and immune precipitation mainly analyzes were used to measure the expression of critical protein p-4ebp1 in mammalian target of rapamycin (mTOR) signaling pathways in the striatum and substantia nigra. RESULTS: Rapamycin can effectively alleviate symptoms of PD. The levels of key protein p-4EBP1 in the striatum and substantia nigra were both significantly higher in PD group compared with control group (P<0.01), while being pretreated with rapamycin, the expression of p-4EBP1 in the striatum and substantia nigra were both decreased obviously (P<0.01). CONCLUSIONS: p-4EBP1 protein may be involved in the pathogenesis of PD via mTOR signaling pathway. Inhibited mTOR-4EBP1 pathways could make a certain protective effect for the acute attack of PD induced by MPTP.