Pten Deletion in Adult Neural Stem/Progenitor Cells Enhances Constitutive Neurogenesis

被引:214
作者
Gregorian, Caroline [1 ]
Nakashima, Jonathan [1 ]
Le Belle, Janel [1 ]
Ohab, John [2 ]
Kim, Rachel [1 ]
Liu, Annie [1 ]
Smith, Kate Barzan [1 ]
Groszer, Matthias [1 ,3 ]
Garcia, A. Denise [4 ]
Sofroniew, Michael V. [4 ]
Carmichael, Thomas [2 ]
Kornblum, Harley I. [1 ,5 ]
Liu, Xin [1 ,3 ]
Wu, Hong [1 ]
机构
[1] Univ Calif Los Angeles, David Geffen Sch Med, Dept Mol & Med Pharmacol, Los Angeles, CA 90095 USA
[2] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurol, Los Angeles, CA 90095 USA
[3] Univ Calif Los Angeles, David Geffen Sch Med, Dept Pathol & Lab Med, Los Angeles, CA 90095 USA
[4] Univ Calif Los Angeles, David Geffen Sch Med, Dept Neurobiol, Los Angeles, CA 90095 USA
[5] Univ Calif Los Angeles, David Geffen Sch Med, Semel Inst, Los Angeles, CA 90095 USA
基金
美国国家卫生研究院;
关键词
SEZ; PTEN; neurogenesis; olfactory; neural repair; poststroke; TUMOR-SUPPRESSOR GENE; LHERMITTE-DUCLOS-DISEASE; RAT OLFACTORY-BULB; STEM-CELLS; SUBVENTRICULAR ZONE; NEURONAL PRECURSORS; NEUROBLASTS MIGRATE; GERMLINE MUTATIONS; GENERATED NEURONS; MAMMALIAN BRAIN;
D O I
10.1523/JNEUROSCI.3095-08.2009
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
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.
引用
收藏
页码:1874 / 1886
页数:13
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