Hypoxia Induces Alzheimer-like Learning And Memory Impairment And Its Underlying Mechanism

Alzheimer's disease (AD) is a progressively neurodegenerative disorder characterized histopathologically by the formation of numerous senile plaques and neurofibrillary tangles. In the past three decades, neurofibrillary tangles hypothesis is one of the focuses of AD pathogenesis research. The imbalance between protein kianse and protein phosphatse is considered as the main reason for neurofibrillary tangles. Hypoxia as a stress increases a number of protein phosphatses, and kinases, activity. Whether hypoxia can cause hyperphosphorylation of Tau by altering the activity of esterase and kinase that is not elucidated. Objective: To study the effect of hypoxia on phosphorylation of Tau protein. Materials and Methods: 40 Sprague Dawley rats were randomly divided into 5 groups, namely the control group, the one-week-hypoxia group, the two-week-hypoxia group, the four-week-hypoxia group, the eight-week-hypoxia group. The rats of the hypoxia groups were put into the hypoxia chamber filled with 11 percents of oxygen and 89 percents of nitrogen for six hours everyday, and last for one week, two weeks, four weeks, eight weeks respectively. Morris water maze was used to test the learning and spatial memory of the rats. Results: Compared with the control, The escape latency of the hypoxia-treated groups was analyzed had a significant increase (P<0.05). The phosphorylation of tau at Ser396 and Ser404 in the 4-week-hypoxia group increases, compared to the control (P<0.05). The data of western bloting also indicates that the activity of GSK3βwas heightened and the activity of PP2A was lowered . Immunohistochemistry shows distribution of the increased phosphorylation of tau at Ser396 in CA3 regions of the hippocampus. Conclusion: Hypoxia damaged caused hyperphosphorylation of Tau at Ser396 and Ser404 through activating GSK3βand inhibiting PP2A, and cause the learning and spatial memory damage.