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

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.

GLP-1 agonist Liraglutide prevents MK­801-induced schizophrenia­like behaviors and BDNF, CREB, p-CREB, Trk-B expressions in the hippocampus and prefrontal cortex in Balb/c mice.

Glucagon-like peptide 1 (GLP-1) agonists are among the agents that can be used to treat type 2 diabetes mellitus, and they have also been reported to have neuroprotective effects. This study examined the effects of GLP-1 agonist Liraglutide on CREB, BDNF, Trk-B expression and emotional/cognitive behaviors in an experimental schizophrenia-like behavior model induced by MK-801. MK-801 (0.25 mg/kg, 0.1 ml/kg body weight) and/or Liraglutide (300 mcg/kg) were injected intraperitoneally once a day for 7 weeks into 8-10 weeks old male Balb/c mice (n = 78). Mice were randomly divided into 5 groups: Saline+Saline, MK-801 +Saline, Liraglutide+Saline, MK-801 +Liraglutide co-treatment, and Liraglutide+MK-801 co-treatment. A Morris water maze test, an elevated plus maze test, and an open field test were performed after injection. Western blots were performed on mice' hippocampus and PFC for BDNF, Trk-B, CREB, and p-CREB expression. Our study found that MK-801 impaired emotional and cognitive functions in mice. MK-801 administration did not affect Liraglutide's positive effects on spatial learning and memory activity in the Liraglutide+MK-801 group. Liraglutide administration (Liraglutide+MK-801 group) improved the BDNF/Trk-B and p-CREB/CREB ratio in the hippocampus, and the p-CREB/CREB ratio in the PFC to the control group level. The negative effects of MK-801 on cognitive behavior were not reversed by Liraglutide in the MK-801 +Liraglutide group. In conclusion, Liraglutide does not affect NMDA receptor blockade-induced emotional and cognitive behaviors. However, it has a protective effect against cognitive impairment. Furthermore, it is possible that the GLP-1 receptors in the hippocampus and PFC are involved in the modulation of NMDA receptor activity through CREB activation/deactivation.