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

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-1,2,3,6tetrahydropyridine (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.

The neuroprotection of hyperoside in MPP+/MPTP -induced Parkinson’s disease model

“…Some neurotrophic factors promote tissue repair and regeneration after nerve injury, which exerts anti-in ammatory, antiapoptotic and axon regeneration effects [40]. Moreover, BDNF alleviated mitochondrial dysfunction and enhanced the Complex I activity in MPTP mice [41]. Similarly, with the previous research [42,43], our study found that neurotrophic factors GDNF, BDNF and CDNF decreased signi cantly in both MPP + and MPTP models.…”

Ginsenosides can target brain-derived neurotrophic factor to improve Parkinson's disease

“…91 Injection of adeno-associated virus with the BDNF gene mitigates mitochondrial damage, cognitive disorders, and loss of dopaminergic neurons more effectively in PD mice. 92 Exercise can improve motor and cognitive impairments by regulating BDNF in PD patients. 93 Through intranasal delivery of BDNF to the target area of the brain, the immunoreactivity of tyrosine hydroxylase was significantly increased, concomitant with improved locomotory function in PD mice.…”

The role of brain derived neurotrophic factor in central nervous system

“…BDNF supports the midbrain dopaminergic neurons surviving, promotes differentiation, and protects dopamine neurons from neurotoxins ( Minichiello et al, 2002 ). BDNF overexpression alleviated motor deficits and cognitive impairment in MPTP-induced PD mice through mitigating mitochondrial damage ( Chang and Wang, 2021 ). What’s more, BDNF level was significantly decreased in the colon of MPTP-treated group compared to the vehicle-treated group, indicating a role of BDNF in the gut-brain axis in PD ( Choi et al, 2021 ).…”