Role of sirt3 in molecular mechanism of melatonin protecting dopaminergic neurons in Parkinson' s disease / 中国药理学通报

ABSTRACT

Aim To investigate the role of SIRT3 in the molecular mechanism of melatonin protecting do-paminergic neurons in Parkinson' s disease ( PD). Methods Forty-eight mice were randomly divided into control group, model group and treatment group. The mice in treatment group received intraperitoneal injection of melatonin (10 mg • kg"1) and MPTP (30 mg • kg ~1). The mice in model group only received intraperitoneal injection of MPTP (30 mg • kg~1 ) , and the mice in control group received the same a-mount of normal saline. Melatonin was administered continuously for 14 days. The expressions of TH and lba-1 in substantia nigra were analyzed by immunohis-tochemistry. The levels of oxidative stress ( ROS, MDA, SOD) and inflammatory factors (TNF-a, IL-lp) in the midbrain were measured by ELISA. SIRT3 mRNA level was analyzed by qRT-PCR, and protein expression level was detected by immunocytochemistry assay and Western blot. Results Compared to control group, the TH expression decreased and Iba-1 expression increased in the substantia nigra, the oxidative stress and inflammatory injury in the midbrain were significantly enhanced, the SIRT3 mRNA and protein levels in the substantia nigra obviously declined, the SOD2 protein expression was also dramatically reduced, and the iNOS protein expression was elevated in model group; the differences between the groups were all statistically significant ( P < 0. 05 ). After treatment with melatonin, the TH expression increased, Iba-1 expression decreased, oxidative stress and inflammatory injury markedly decreased, SIRT3 mRNA and protein levels were elevated, SOD2 protein expression was up-regulated, and iNOS protein expression was down-regulated in treatment group. Compared to model group, the differences were all statistically significant ( P < 0.05). Conclusions Melatonin can counteract the damage of dopaminergic neurons by up-regulating the expression of SIRT3 in PD animal model. Its mechanisms of action are related to inhibiting microglia activation, and alleviating oxidative stress and inflammation injury.