Investigation of the protective effect of long-term exercise on molecular pathways and cognitive behaviors in alzheimer disease model

The role of exercise in the treatment and prevention of neurodegenerative diseases continues to remain unclear despite studies. In our study, the protective effect of treadmill exercise on molecular pathways and cognitive behaviors was investigated in the Alzheimer disease model induced by scopolamine. For that purpose, male Balb/c mice (n=69) which was separated from their mothers on day 21 were subjected to treadmill exercise for 12 weeks. In the last 4 weeks (28 days) of the exercise, scopolamine injection (2mg/kg, once a day) was administered intraperitoneally to the mice. Following the injection emotional and cognitive behaviors were evaluated with open field test and morris water maze test. The hippocampus and prefrontal cortex of the mice were isolated and BDNF, TrkB, p-GSK3ßSer389 levels were evaluated by Western blotting, and APP and Aß-40 levels were analyzed by immunohistochemistry. In our study, scopolamine administration in mice caused impairment in cognitive and emotional functions. Scopolamine caused a decrease in p-GSK3ßSer389, BDNF (p=0.014) and TrkB (p=0.01) levels in the hippocampus. In the prefrontal cortex, p-GSK3ßSer389 and BDNF (p=0.014) levels decreased, while TrkB (p=0.013) levels increased. As a result of immunohistochemical analysis, it was found that APP and Aß-40 in the hippocampus and prefrontal cortex increased in neuronal and perineuronal areas with scopolamine administration. In our study, it was found that long-term exercise had protective effects against impairment in cognitive and emotional functions. There was an increase in p-GSK3ßSer389, BDNF (p=0.01) and TrkB (p=0.02) levels in the hippocampus in the treadmill exercise group. There were also increases in p-GSK3ßSer389, BDNF (p=0.02) and TrkB (p=0.01) levels in the prefrontal cortex. In the immunohistochemical analysis it was observed that Aß-40 and APP were decreased in the exercise groups. In conclusion, long-term treadmill exercise may have a protective effect against the impairment in cognitive and emotional behaviors induced by scopolamine. It can be suggested that this protective effect is mediated by increased BDNF level and GSK3ßSer389 phosphorylation. Key Words: Alzheimer's disease, Amyloid beta, BDNF, Exercise, p-GSK3ßSer389, Scopolamine