美國(guó)斯坦福大學(xué)醫(yī)學(xué)院的研究人員Anne Brunet等人對(duì)老鼠模型研究發(fā)現(xiàn),，一個(gè)與壽命相關(guān)的基因能夠影響大腦神經(jīng)干細(xì)胞的功能。這項(xiàng)研究還說(shuō)明在衰老過(guò)程中,，該基因或許對(duì)維持認(rèn)知功能有重要的作用,。這篇研究報(bào)告發(fā)表在11月6日的Cell Stem Cell雜志上。
大腦神經(jīng)干細(xì)胞有兩種不同的命運(yùn)：一類(lèi)維持自我更新,，另一類(lèi)形成新的神經(jīng)元以及少突膠質(zhì)細(xì)胞(oligodendrocytes)和星形膠質(zhì)細(xì)胞(astrocytes),。老鼠在衰老過(guò)程中，大腦神經(jīng)干細(xì)胞庫(kù)開(kāi)始萎縮,，新生神經(jīng)元越來(lái)越少,，從而使認(rèn)知能力和感覺(jué)功能逐漸喪失。
該課題組對(duì)FoxO轉(zhuǎn)錄因子家族(參與細(xì)胞增殖,，分化和凋亡)進(jìn)行研究,，研究人員通過(guò)敲除老鼠FoxO3基因，想確認(rèn)該基因是否參與調(diào)控神經(jīng)干細(xì)胞庫(kù),。在試驗(yàn)中,，Brunet選擇了三個(gè)年齡階段的老鼠：出生1天(新生兒期)，3個(gè)月大(青年期),，1年(中年期)實(shí)施基因敲除,。他們發(fā)現(xiàn),，缺失FoxO3基因的青年期和中年期的老鼠和對(duì)照組(未進(jìn)行基因敲除)老鼠相比，神經(jīng)干細(xì)胞中FoxO3調(diào)節(jié)蛋白的數(shù)量要少得多,。而對(duì)新生老鼠來(lái)說(shuō),，是否缺失FoxO3基因影響不大，這說(shuō)明,，F(xiàn)oxO3調(diào)節(jié)因子只對(duì)成年期有影響,。
研究人員還發(fā)現(xiàn)，缺失FoxO3基因的成年老鼠大腦中極少量的干細(xì)胞比正常老鼠能更快速產(chǎn)生大量的神經(jīng)細(xì)胞前體(neural cell precursors)——可以分化為新生神經(jīng)元,。而且缺失FoxO3基因的成年老鼠一般比對(duì)照組重,。
對(duì)培養(yǎng)皿中神經(jīng)干細(xì)胞觀察發(fā)現(xiàn)，青年期和中年期老鼠的神經(jīng)干細(xì)胞中缺少FoxO3調(diào)節(jié)蛋白,，但新生兒期正常,，這或許與三個(gè)時(shí)期神經(jīng)干細(xì)胞自我更新以及形成神經(jīng)元的能力不同有關(guān)。（生物谷Bioon.com）
生物谷推薦原始出處：
Cell Stem Cell,6 November 2009 doi:10.1016/j.stem.2009.09.014
FoxO3 Regulates Neural Stem Cell Homeostasis
Valérie M. Renault1, Victoria A. Rafalski1, 2, Alex A. Morgan3, 6, Dervis A.M. Salih1, Jamie O. Brett1, Ashley E. Webb1, Saul A. Villeda1, 2, 7, Pramod U. Thekkat1, Camille Guillerey1, Nicholas C. Denko4, Theo D. Palmer5, Atul J. Butte3, 6 and Anne Brunet1, 2, ,
1 Department of Genetics, Stanford University, Stanford, CA 94305, USA
2 Neurosciences Program, Stanford University, Stanford, CA 94305, USA
3 Biomedical Informatics Program, Stanford University, Stanford, CA 94305, USA
4 Department of Radiation Oncology, Stanford University, Stanford, CA 94305, USA
5 Department of Neurosurgery, Stanford University, Stanford, CA 94305, USA
6 Departments of Pediatrics and Medicine, Lucile Packard Children's Hospital, Stanford University, Stanford, CA 94304, USA
In the nervous system, neural stem cells (NSCs) are necessary for the generation of new neurons and for cognitive function. Here we show that FoxO3, a member of a transcription factor family known to extend lifespan in invertebrates, regulates the NSC pool. We find that adult FoxO3−/− mice have fewer NSCs in vivo than wild-type counterparts. NSCs isolated from adult FoxO3−/− mice have decreased self-renewal and an impaired ability to generate different neural lineages. Identification of the FoxO3-dependent gene expression profile in NSCs suggests that FoxO3 regulates the NSC pool by inducing a program of genes that preserves quiescence, prevents premature differentiation, and controls oxygen metabolism. The ability of FoxO3 to prevent the premature depletion of NSCs might have important implications for counteracting brain aging in long-lived species.
