Amyloid β-peptide, a major component of senile plaques in Alzheimer's disease, has been implicated in neuronal cell death and cognitive impairment. Recently, studies have shown that the pathogenesis of cerebral ischemia is closely linked with Alzheimer's disease. In this study, a rat model of global cerebral ischemia-reperfusion injury was established via occlusion of four arteries; meanwhile, fibrillar amyloid β-peptide was injected into the rat lateral ventricle. The Morris water maze test and histological staining revealed that administration of amyloid β-peptide could further aggravate impairments to learning and memory and neuronal cell death in the hippocampus of rats subjected to cerebral ischemia-reperfusion injury. Western blot showed that phosphorylation of tau protein and the activity of glycogen synthase kinase 3β were significantly stronger in cerebral ischemia-reperfusion injury rats subjected to amyloid β-peptide administration than those undergoing cerebral ischemia-reperfusion or amyloid β-peptide administration alone. Conversely, the activity of protein phosphatase 2A was remarkably reduced in rats with cerebral ischemia-reperfusion injury following amyloid β-peptide administration. These findings suggest that amyloid β-peptide can potentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cognitive impairment.Research Highlights
(1) This study combined intracerebroventricular injection of amyloid β-peptide with cerebral ischemia and reperfusion to establish a new animal model of Alzheimer's disease. We found that a single injection of amyloid β-peptide alone could not impair learning and memory abilities in rats or cause death of hippocampal neurons. However, intracerebroventricular injection of amyloid β-peptide lowing cerebral ischemia and reperfusion could aggravate learning and memory in rats and cause nerve cell death.Research Highlights
(2) In this study, the synergistic effect of amyloid β-peptide and cerebral ischemia-reperfusion injury exacerbated nerve damage by inducing glycogen synthase kinase 3β and protein phosphatase 2A activity, which resulted in the phosphorylation of tau protein.