[Treadmill exercise improves constipation in mice with chronic Parkinson's disease through activating autophagy]

This study aimed to explore the effects and molecular mechanisms of 8-week treadmill exercise on constipation symptoms in mice with chronic Parkinson's disease (PD). Forty C57BL/6 mice were randomly divided into four groups: control group, model (PD) group, 8-week treadmill exercise (PD+Ex) group, and 8-week treadmill exercise+3-methyladenine (3MA) (PD+Ex+3MA) group, with n = 10 in each group. A chronic PD mouse model was prepared using 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) combined with probenecid (MPTP/p). The PD+Ex group underwent 8 weeks of treadmill exercise training, while the PD+Ex+3MA group received an additional 5 weeks of 3MA intraperitoneal injection (simultaneously with modeling). Constipation symptoms were evaluated using indicators such as defecation parameters, colon length, and colon to body weight ratio. Immunofluorescence staining was used to detect α-synuclein (α-syn) deposition in the colon. RT-qPCR was used to detect the mRNA expression levels of key enzymes of neurotransmitters in the colon, and Western blot was used to detect pathological and autophagy-related protein expression levels. The results showed that, compared with the control group, the PD group mice exhibited motor dysfunction and significant constipation symptoms. In the PD group, the protein expression of tyrosine hydroxylase (TH) in the striatum was significantly downregulated, while α-syn deposition in the colon was significant and its protein expression was significantly up-regulated. The mRNA expression of neuronal nitric oxide synthase (nNOS) was up-regulated, while the expression levels of TH protein and choline acetyltransferase (ChAT) mRNA were down-regulated in the colon. The protein expression of p62 was up-regulated, and the protein expression levels of Beclin1 and LC3II were down-regulated in the colon. After treadmill exercise intervention, all the above changes in the PD group were significantly improved, and autophagy inhibitor 3MA could counteract these improving effects of treadmill exercise intervention. These results suggest that 8-week treadmill exercise can improve constipation symptoms in MPTP/p-induced chronic PD mice, and its protective effect may be achieved by activating autophagy.