Aerobic Exercise Activates Bdnf/creb Pathway And Enhances Behavior Features In Parkinson’S Disease Mice

Abstract

Neurotrophic factors are associated with neurological disorders including Parkinson’s disease (PD). However, the role of brain-derived neurotrophic factor (BDNF) and the molecular mechanism of relative signaling mediating neuron homeostasis by exercise in PD are unclear. PURPOSE: The effect of exercise on the behavior of PD mice was analyzed, to observe the expression of neurotrophic factor of BDNF mediated by exercise, and to analyze the regulation of BDNF mediated by ERK1/2-CREB pathway. METHODS: After 8 weeks of training, the final group was as follows: Quiet + Saline group (WT), Exercise + Saline group (WE), Quiet + MPTP group (M), Exercise + MPTP group (ME). Mice in M and ME group were injected with intraperitoneal MPTP once each day for 7 times, mice in WT and WE groups received the same dose of saline intraperitoneal injection at the same time. The PD model was made, and the behavioral test was carried out, as well the molecular features were detected by immunofluorescence and Western blot. RESULTS: (1) In the behavior experiment, for step length M group decreased significantly (P < 0.05), but M group ME was significantly increased (P < 0.05) for rotation time; In open field experiment, the central activity track and total distance of WT group were higher than those of M group (P < 0.05). Although the central activity track and total distance of ME group were higher than that of M group, there was no significant difference (P > 0.05). (2) Tyrosine hydroxylase (TH) activity was detected by immunofluorescence and Western blot. Compared with WT, the expression of TH protein in M group was significantly lower (P < 0.01), while TH protein expression was increased in ME group compared with M group (P < 0.05). (3) Compared with group M, BDNF and TrkB protein expression increased after exercise training (P < 0.05). The protein expression of downstream signal marker ERK (P < 0.01), P-ERK (P < 0.01) and P-CREB (P < 0.05) were also up-regulated. CONCLUSION: Exercise training increases the neurotrophic factor BDNF expression, and activates the BDNF-CREB signaling pathway in central nervous system, in which exercise promotes the motor behavior, and alleviates the pathological features in PD mice. Key words: aerobic exercise; motor features; Tyrosine hydroxylase (TH); Neurotrophic factor BDNF; Parkinson’s disease