| First Author | Zhang X | Year | 2013 |
| Journal | Neurobiol Aging | Volume | 34 |
| Issue | 3 | Pages | 663-78 |
| PubMed ID | 22795785 | Mgi Jnum | J:194433 |
| Mgi Id | MGI:5473762 | Doi | 10.1016/j.neurobiolaging.2012.06.012 |
| Citation | Zhang X, et al. (2013) Prenatal hypoxia may aggravate the cognitive impairment and Alzheimer's disease neuropathology in APPSwe/PS1A246E transgenic mice. Neurobiol Aging 34(3):663-78 |
| abstractText | Most cases of Alzheimer's disease (AD) arise through interactions between genetic and environmental factors. It is believed that hypoxia is an important environmental factor influencing the development of AD. Our group has previously demonstrated that hypoxia increased beta-amyloid (Abeta) generation in aged AD mice. Here, we further investigate the pathological role of prenatal hypoxia in AD. We exposed the pregnant APP(Swe)/PS1(A246E) transgenic mice to high-altitude hypoxia in a hypobaric chamber during days 7-20 of gestation. We found that prenatal hypoxic mice exhibited a remarkable deficit in spatial learning and memory and a significant decrease in synapses. We also documented a significantly higher level of amyloid precursor protein, lower level of the Abeta-degrading enzyme neprilysin, and increased Abeta accumulation in the brain of prenatal hypoxic mice. Finally, we demonstrated striking neuropathologic changes in prenatal hypoxic AD mice, showing increased phosphorylation of tau, decreased hypoxia-induced factor, and enhanced activation of astrocytes and microglia. These data suggest that although the characteristic features of AD appear later in life, hypoxemia in the prenatal stage may contribute to the pathogenesis of the disease, supporting the notion that environmental factors can trigger or aggravate AD. |
