Investigation of the protective effect of long-term exercise on molecular pathways and behaviours in scopolamine induced alzheimer's disease-like condition

• Published in: Brain research 2023-09, Vol.1814, p.148429-148429, Article 148429
• Main Authors: Kose, Seda, Kutlu, Meltem Donmez, Kara, Samet, Polat, Sait, Akillioglu, Kubra
• Format: Article
• Language: English
• Subjects: Alzheimer's disease; Amyloid beta; BDNF; Exercise; p-GSK3ßSer389; Scopolamine
• ISSN: 0006-8993; 1872-6240
• DOI: 10.1016/j.brainres.2023.148429

[Display omitted] •Cognitive-emotional functions are impaired in scopolamine-induced AD model in mice.•Long-term exercise reduced APP and Aß-40 levels induced by scopolamine.•Exercise increases BDNF, TrkB and pGSK3ßSer389 levels in hippocampus.•Exercise has a protective effect against anxiety-like behaviors and impaired memory.•The effects of exercise are may be mediated by the p38MAPK/GSK3ßSer389 pathway. Despite research, the role of exercise in treatment and prevention of neurodegenerative diseases remains unclear. Our study, investigated that protective effect of treadmill exercise on molecular pathways and cognitive behaviours in a scopolamine-induced model of Alzheimer's disease. For that purpose, male Balb/c mice subjected to exercise for 12 weeks. During the last 4 weeks of exercise, mice were given an injection of scopolamine (2 mg/kg). Following injection, open field test and Morris water maze test were used to assess emotional-cognitive behaviour. Hippocampus and prefrontal cortex of mice were isolated, and levels of BDNF, TrkB, and p-GSK3ßSer389 were assessed by western blotting, and levels of APP and Aß-40 were analysed by immunohistochemistry. In our study, scopolamine administration increased anxiety-like behaviour in open field test, while negatively affecting spatial learning and memory in Morris water maze test. We found that exercise had a protective effect against cognitive and emotional decline. Scopolamine decreased levels of p-GSK3ßSer389, BDNF in hippocampus and prefrontal cortex.Whereas TrkB decreased in hippocampus and increased in prefrontal cortex. There was an increase in p-GSK3ßSer389, BDNF, TrkB in the hippocampus, and p-GSK3ßSer389, BDNF in the prefrontal cortex in the exercise + scopolamine group. Immunohistochemical analysis showed that scopolamine administration increased APP and Aß-40 in hippocampus and prefrontal cortex in neuronal and perineuronal areas whereas Aß-40 and APP were reduced in exercise + scopolamine groups. In conclusion, long-term exercise may have a protective effect against scopolamine-induced impairments in cognitive-emotional behaviour. It can be suggested that this protective effect is mediated by increased BDNF levels and GSK3ßSer389 phosphorylation.