Aerobic exercise improves motor function and striatal MSNs-Erk/MAPK signaling in mice with 6-OHDA-induced Parkinson's disease

In Parkinson's disease (PD) state, with progressive loss of dopaminergic neurons in the substantia nigra, the striatal dopamine (DA) and glutamate (Glu) levels change, resulting in dysfunction of basal ganglia motor regulation. The PD patient presents motor dysfunction such as resting tremor, bradykinesia, and muscular rigidity. To investigate the mechanism of aerobic exercise to improve PD-related motor dysfunction, in the current study, 6-hydroxydopamine (6-OHDA) was used to induce the PD mice model, and the motor function of PD mice was comprehensively evaluated by open-field test, rotarod test, and gait test. The co-expression of prodynorphin (PDYN) and proenkephalin (PENK) with extracellular signal-regulated kinase (Erk1/2) and phosphorylation Erk1/2 (p-Erk1/2) were detected by double-labeling immunofluorescence. The results showed that a 4-week aerobic exercise intervention could effectively improve the motor dysfunction of PD mice. Moreover, it was found that the expressions of Erk1/2 and p-Erk1/2 in the dorsal striatum (Str) of PD mice were significantly increased, and the number of positive cells co-expressed by Erk1/2, p-Erk1/2, and PENK was significantly higher than PDYN. The above phenomenon was reversed by a 4-week aerobic exercise intervention. Therefore, this study suggests that the mechanism by which aerobic exercise improves PD-related motor dysfunction may be related to that the aerobic exercise intervention alleviates the activity of extracellular signal-regulated kinase/mitogen-activated protein kinases (Erk/MAPK) signaling pathway in striatal medium spiny neurons expressing D2-like receptors (D2-MSNs) of PD mice by regulating the striatal DA and Glu signaling.