Background: Parkinson's disease (PD) is one of the most common neurodegenerative disorders that seriously impair the life quality and survival of patients. Herein, we aim to investigate the neuroprotective roles of brain-derived neurotrophic factor (BDNF) in PD mice and reveal the underlying mechanisms. BDNF overexpression was achieved via the injection of adeno-associated viruses (AAV) with BDNF gene. Methods: PD mouse model was established by 1-methyl-4-phenyl-1,2,3,6tetrahydropyridine (MPTP) treatment. Tests of rotarod, pole, open field, and novel object recognition were conducted to evaluate the motor and cognitive functions of treated mice. Results: Mitochondrial impairment, mitochondrial respiratory chain enzymes, and tyrosine hydroxylase (TH)-positive dopaminergic neurons were detected to uncover the molecular mechanism. BDNF overexpression attenuated motor deficits and cognitive impairment in MPTP-induced PD mice. Mechanistically, BDNF mitigated mitochondrial impairment increased the activity of respiratory chain Complex I and II+III, and finally alleviated TH-positive dopaminergic neuron loss in MPTP-induced PD mice. Conclusion:This study highlights the potential of BDNF as a therapeutic candidate for the treatment of mitochondrial impairment-associated neurodegenerative diseases.

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