Protective effect of folate and vitamin B12 on Alzheimer-like pathological changes in brain of aged rats with hyperhomocysteinemia

AIM:To explore the effect of hyperhomocysteinemia on the Alzheimer-like pathological changes in the brain of aged rat. METHODS:The rats were treated with homocysteine(Hcy) by intravenous injection through vena caudalis with or without a simultaneous supplementation of folate and Vitamin B₁₂(FB) in the drinking water for 28 weeks. The distribution and aggregation of tau protein were detected by Bielschowsky silver staining. Western blotting was used to determine the protein levels of tau phosphorylation, glycogen synthase kinase 3β(GSK-3β) and protein phosphatase 2A(PP2A). RESULTS:Treatment with Hcy induced hyperhomocysteinemia in aged rats and resulted in the formation of neurofibrillary tangles in the brain. Supplementation of FB effectively reduced the tangles. Hyperhomocysteinemia also induced Alzheimer-like tau hyperphosphorylation at multiple sites(Ser^199/202and Ser³⁹⁶). Hyperhomocysteinemia activated GSK-3β and inhibited the activity of PP2A. Supplementation of FB alleviated the changes of tau and the activities of GSK-3β and PP2A. CONCLUSION:Supplementation of FB ameliorates the hyperhomocysteinemia-induced Alzheimer-like pathological changes of tau protein possibly through regulating the activity of GSK-3β and PP2A in aged rats.