Neurogenic effects of rotarod walking exercise in subventricular zone, subgranular zone, and substantia nigra in MPTP-induced Parkinson’s disease mice

Parkinson’s disease (PD) is the second most common neurodegenerative disease after Alzheimer’s disease, and its incidence is predicted to increase worldwide. Striatal dopamine depletion caused by substantia nigra (SN) degeneration is a pathological hallmark of PD and is strongly associated with cardinal motor and non-motor symptoms. Previous studies have reported that exercise increases neuroplasticity and promotes neurorestoration by increasing neurotrophic factors and synaptic strength and stimulating neurogenesis in PD. In the present study, we found that rotarod walking exercise, a modality of motor skill learning training, improved locomotor disturbances and reduced nigrostriatal degeneration in the subacute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. In addition, our exercise regimen improved MPTP-induced perturbation of adult neurogenesis in some areas of the brain, including the subventricular zone, subgranular zone, SN, and striatum. Moreover, rotarod walking activated the phosphorylation of adenosine monophosphate-activated protein kinase (AMPK) and induced brain-derived neurotrophic factor (BDNF) expression in these regions. The results suggest that motor skill learning training using rotarod walking improves adult neurogenesis and restores motor performance by modulating the AMPK/BDNF pathway. Therefore, our findings provide evidence for neuroprotective effects and improved neuroplasticity in PD through motor skill learning training.