Effects of metformin and exercise on Alzheimer's model induced by D-galactose in the rats: A behavioral, histological and BDNF gene study

The objective of the current research is to investigate the cognitive performance of male Alzheimer's disease rats in the context of the combined effects of exercise and metformin. The rats were divided into eight different groups. The Morris water maze (MWM) and the open field test (OFT) were employed to assess the cognitive functionality and motor activity of rats, respectively. The hippocampus of rats was subjected to histological evaluation, and expression of brain-derived neurotrophic factor (BDNF) was measured using the real-time polymerase chain reaction (RT-PCR) method. On concluding day of training, the d-gal-met100-exe group (D-galactose plus optimized 100mg/kg of metformin along with exercise) exhibited a diminished duration in the target quadrant ( P < 0.0001) and covered a shorter distance to find the platform ( P = 0.0004). On the day of the test, the distance covered in the target quadrant decreased in the d-gal group that received 120mg/kg of D-galactose ( P = 0.0186) and significantly increased in the d-gal-met100-exe group compared to the d-gal group ( P = 0.0002). The OFT indicated no substantial variations in distance or overall speed across the groups, suggesting that metformin did not affect motor activity. Based on the histology findings, in the d-gal-met100-exe group, fewer pyramidal cells led to less neuronal damage ( P < 0.0001). In contrast, the BDNF gene in the hippocampus of the aforementioned group rose considerably as compared to the d-gal group ( P = 0.0002). In general, the combined administration of metformin and exercise had a greater effect on enhancing memory and learning in Alzheimer's rats.