Melatonin attenuates MPP+-induced autophagy via heat shock protein in the Parkinson's disease mouse model.

Background: This study investigates the protective properties of melatonin in an in vivo Parkinson's disease (PD) model, focusing on the underlying mechanisms involving heat shock proteins (HSPs).

Methods: Twelve adult male C57BL/6 mice were randomly divided into four groups (normal control, melatonin control, Parkinson's model, and melatonin treatment; n = 3 per group) and housed in a single cage. 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was injected intraperitoneally in the Parkinson's model and treatment groups to establish a subacute PD model, while controls received saline. Limb motor ability was assessed 1 h after the final injection using behavioral tests, including the open field test to evaluate central zone entries and average movement. Dopamine transporter (DAT) expression in the striatum was analyzed by immunohistochemistry, and Western blot was used to measure autophagy proteins and HSP70 levels.

Results: The PD mouse model was successfully established through MPTP stimulation. Compared to the normal control group, the model group showed a significant reduction in the frequency of entering the central zone and average movement. The number of DAT-positive cells in the brain also decreased significantly. The expression levels of HSP70 and CDK5 were significantly lower, while the expression levels of LC3 II /LC3I and p62 increased significantly. In the MT treatment group, both the frequency of entering the central zone and the average movement were significantly higher compared to the model group. DAT-positive cells in the midbrain also increased significantly. The expression levels of HSP70 and CDK5 were significantly elevated, while the expression levels of LC3 II /LC3I and p62 protein were significantly decreased.

Conclusion: Melatonin exerts a protective effect against MPP⁺-induced damage to dopaminergic neurons, presumably by upregulating HSP70, which inhibits neuronal autophagy.