title: Amyloid beta-peptide worsens cognitive impairment following cerebral ischemia-reperfusion injury.
abstract: 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 under-going 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.
authors.affiliation: Research Center of Stem Cells and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China ; State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Bo
authors.initials: B
authors.lastname: Song
authors.affiliation: Research Center of Stem Cells and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China ; Institute of Neurology Disorders, Yuquan Hospital, Tsinghua University, Beijing 100049, China.
authors.forename: Qiang
authors.initials: Q
authors.lastname: Ao
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Niu
authors.affiliation: Research Center of Stem Cells and Regenerative Medicine, School of Medicine, Tsinghua University, Beijing 100084, China.
authors.forename: Qin
authors.initials: Q
authors.lastname: Shen
authors.affiliation: Institute of Neurology Disorders, Yuquan Hospital, Tsinghua University, Beijing 100049, China.
authors.forename: Huancong
authors.initials: H
authors.lastname: Zuo
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Xiufang
authors.initials: X
authors.lastname: Zhang
authors.affiliation: State Key Laboratory of Biomembrane and Membrane Biotechnology, School of Life Sciences, Tsinghua University, Beijing 100084, China.
authors.forename: Yandao
authors.initials: Y
authors.lastname: Gong
keywords: Alzheimer's disease; amyloid β-peptides; brain injury; cerebral ischemia-reperfusion; glycogen synthase kinase 3β; grants-supported paper; neural regeneration; neuroregeneration; phosphorylation; protein phosphatase 2A; tau proteins