Exogenous brain-derived neurotrophic factor attenuates cognitive impairment induced by okadaic acid in a rat model of Alzheimer's disease.

Decreased expression of brain-derived neurotrophic factor (BDNF) plays an important role in the pathogenesis of Alzheimer's disease, and a typical pathological change in Alzheimer's disease is neurofibrillary tangles caused by hyperphosphorylation of tau. An in vivo model of Alzheimer's disease was developed by injecting okadaic acid (2 μL) and exogenous BDNF (2 μL) into the hippocampi of adult male Wister rats. Spatial learning and memory abilities were assessed using the Morris water maze. The expression levels of protein phosphatase 2A (PP2A), PP2Ac-Yp307, p-tau (Thr231), and p-tau (Ser396/404) were detected by western blot assay. The expression levels of BDNF, TrkB, and synaptophysin mRNA were measured by quantitative real-time polymerase chain reaction. Our results indicated that BDNF expression was suppressed in the hippocampus of OA-treated rats, which resulted in learning and memory deficits. Intra-hippocampal injection of BDNF attenuated this OA-induced cognitive impairment. Finally, our findings indicated an involvement of the PI3K/GSK-3β/AKT pathway in the mechanism of BDNF in regulating cognitive function. These results indicate that BDNF has beneficial effect on Alzheimer's disease, and highlight the potential of BDNF as a drug target for treatment of Alzheimer's disease.