期刊
JOURNAL OF NEUROSCIENCE
卷 29, 期 6, 页码 1874-1886出版社
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3095-08.2009
关键词
SEZ; PTEN; neurogenesis; olfactory; neural repair; poststroke
资金
- Miriam and Sheldon Adelson Program in Neural Repair and Rehabilitation
- National Institutes of Health [NS047386, MH65756]
- Brain Tumor Society
- Henry Singleton Brain Cancer Research Program
- James S. McDonnell Foundation Award
- United States Department of Health and Human Services Ruth L. Kirschstein Institutional National Research Service Award [T32 CA09056]
Here we show that conditional deletion of Pten in a subpopulation of adult neural stem cells in the subependymal zone (SEZ) leads to persistently enhanced neural stem cell self-renewal without sign of exhaustion. These Pten null SEZ-born neural stem cells and progenies can follow the endogenous migration, differentiation, and integration pathways and contribute to constitutive neurogenesis in the olfactory bulb. As a result, Pten deleted animals have increased olfactory bulb mass and enhanced olfactory function. Pten null cells in the olfactory bulb can establish normal connections with peripheral olfactory epithelium and help olfactory bulb recovery from acute damage. Following a focal stroke, Pten null progenitors give rise to greater numbers of neuroblasts that migrate to peri-infarct cortex. However, in contrast to the olfactory bulb, no significant long-term survival and integration can be observed, indicating that additional factors are necessary for long-term survival of newly born neurons after stroke. These data suggest that manipulating PTEN-controlled signaling pathways may be a useful step in facilitating endogenous neural stem/progenitor expansion for the treatment of disorders or lesions in regions associated with constitutive neurogenesis.
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