Afaf Sayed Osman, Mohammed Hassan Gad, Amal Ahmed Hareedy, Amal Anwar Mishriki, Eman Abdel Monem Abdel Rasheed

Abstract

Background: Alzheimer’s disease is recognized as the most prevalent form of dementia. GLP-1R agonists improve spatial memory in models of AD. This investigation was done to study the role of sitagliptin on improving memory defects in AD, induced in rats. Methods: 48 adult female albino rats were divided into four groups: Group I: the control normal group. Group II: received i.p. 4.2 mg/kg/day aluminum chloride for 4 weeks. Group III: treatment with 10 mg/kg sitagliptin was started 2 weeks after induction of the model for 4 weeks. Group IV: treatment with donepezil (1 mg/kg) started 2 weeks after induction of the model for 4 weeks. The NOR test and the MWM test were used. Brain amyloid beta (Aβ1–42) levels and malondialdehyde in hippocampal homogenate were assessed and histopathological examination was done. Results: Aluminum chloride injection in rats induced significant deterioration in cognitive function as tested with NOR and MWM tests, and a significant increase was observed in the brain MDA and Aβ1–42 levels, which was associated with the histopathological insults compared with control untreated rats. Treatment with sitagliptin significantly improved the changes of memory, reduced the brain level of MDA and Aβ, and improved the brain pathology compared with the model group. Conclusion: We reached a novel finding of the sitagliptin’s protective effect against the neurodegenerative effect of AD induced by aluminum injection‎.