期刊名称：Proceedings of the National Academy of Sciences
印刷版ISSN：0027-8424
电子版ISSN：1091-6490
出版年度：2010
卷号：107
期号：14
页码：6498-6503
DOI：10.1073/pnas.1001422107
语种：English
出版社：The National Academy of Sciences of the United States of America
摘要：Our previous analyses showed that allopregnanolone (AP{alpha}) significantly increased proliferation of rodent and human neural progenitor cells in vitro. In this study, we investigated the efficacy of AP{alpha} to promote neurogenesis in the hippocampal subgranular zone (SGZ), to reverse learning and memory deficits in 3-month-old male triple transgenic mouse model of Alzheimer's (3xTgAD) and the correlation between AP{alpha}-induced neural progenitor cell survival and memory function in 3xTgAD mice. Neural progenitor cell proliferation was determined by unbiased stereological analysis of BrdU incorporation and survival determined by FACS for BrdU+ cells. Learning and memory function was assessed using the hippocampal-dependent trace eye-blink conditioning paradigm. At 3 months, basal level of BrdU+ cells in the SGZ of 3xTgAD mice was significantly lower relative to non-Tg mice, despite the lack of evident AD pathology. AP{alpha} significantly increased, in a dose-dependent manner, BrdU+ cells in SGZ in 3xTgAD mice and restored SGZ proliferation to normal magnitude. As with the deficit in proliferation, 3xTgAD mice exhibited deficits in learning and memory. AP{alpha} reversed the cognitive deficits to restore learning and memory performance to the level of normal non-Tg mice. In 3xTgAD mice, AP{alpha}-induced survival of neural progenitors was significantly correlated with AP{alpha}-induced memory performance. These findings suggest that early neurogenic deficits, which were evident before immunodetectable A{beta
