Brain‐derived neurotrophic factor attenuates cognitive impairment and motor deficits in a mouse model of Parkinson's disease

Abstract

Abstract 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‐1,2,3,6‐tetrahydropyridine (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.

Keywords

• BDNF
• behavior
• dopaminergic neuron
• mitochondria
• Parkinson's disease