Abstract:

Amyloid β-peptide, a major component of senile plaques in Alzheimer’s disease, has been impli-cated 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 is-chemia-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 po-tentiate tau phosphorylation induced by cerebral ischemia-reperfusion and thereby aggravate cog-nitive impairment.

Key words: neural regeneration, brain injury, cerebral ischemia-reperfusion, Alzheimer’s disease, amyloid β-peptides, tau proteins, glycogen synthase kinase 3β, protein phosphatase 2A, phosphorylation, grants-supported paper, neuroregeneration