通過對(duì)小鼠進(jìn)行研究,，近日約翰霍普金斯大學(xué)的研究者揭示了，大腦中的干細(xì)胞可以如何對(duì)學(xué)習(xí)能力,、記憶力和情緒進(jìn)行調(diào)節(jié)來決定這些大腦中的剩余干細(xì)胞是否繼續(xù)休眠還是產(chǎn)生新的腦細(xì)胞來作為補(bǔ)充,。大腦干細(xì)胞可以在神經(jīng)元之間“監(jiān)聽”其化學(xué)信息來發(fā)現(xiàn)什么對(duì)神經(jīng)系統(tǒng)施壓以及這些干細(xì)胞該如何行動(dòng)。
相關(guān)研究成果刊登在了7月29日的國際雜志Nature上,。干細(xì)胞檢測到的這種間接的談話包括神經(jīng)元突觸泄露所引發(fā)的神經(jīng)遞質(zhì)輸出的化學(xué)信號(hào),，大腦細(xì)胞末端的結(jié)構(gòu)可以促進(jìn)信號(hào)交流,，這些神經(jīng)遞質(zhì)可以從一個(gè)神經(jīng)元那里釋放然后被另一個(gè)神經(jīng)元所檢測到,，最終引發(fā)神經(jīng)元的電荷改變。
為了研究哪種神經(jīng)遞質(zhì)大腦干細(xì)胞可以進(jìn)行檢測,，研究者使用小鼠的大腦進(jìn)行研究,，將電極吸附至干細(xì)胞上，測定其在添加神經(jīng)遞質(zhì)后的電荷改變,。當(dāng)研究者添加神經(jīng)遞質(zhì)GABA后,，干細(xì)胞的電荷發(fā)生了改變，因此這就表明,，干細(xì)胞可以檢測到GABA（γ-氨基酪酸）的信息,，GABA是一種信號(hào)抑制產(chǎn)物。
為了發(fā)現(xiàn)那種信息GABA可以損傷大腦干細(xì)胞,，研究者使用遺傳的方法來從大腦干細(xì)胞中移除了GABA受體基因,。對(duì)缺失GABA受體基因的大腦干細(xì)胞進(jìn)行顯微觀察5天以上,，研究者發(fā)現(xiàn)細(xì)胞可以重復(fù)折疊自身，或者產(chǎn)生神經(jīng)膠質(zhì)細(xì)胞,，來供給大腦中的神經(jīng)元細(xì)胞,。下一步，研究者用地西泮（抗精神失常藥,，可以像GABA一樣來激活其受體）來處理小鼠,，研究者檢測了第二天和第七天小鼠的地西泮使用情況，并且統(tǒng)計(jì)了未處理小鼠和處理小鼠大腦的神經(jīng)干細(xì)胞的數(shù)量,。他們發(fā)現(xiàn),，處理過的小鼠相比未處理的小鼠大腦中存在許多休眠的干細(xì)胞。
最終,，研究者為了觀察是否這種干細(xì)胞控制機(jī)制可以和其經(jīng)歷的過程有關(guān),，研究者通過孤立孤立小鼠來制造壓力，同樣在缺少GABA受體的小鼠中也進(jìn)行相似操作,。一周后,，正常小鼠的干細(xì)胞數(shù)量上升了，然而缺少GABA的小鼠卻沒有表現(xiàn)出上升的趨勢,。
GABA的通訊可以清晰地傳遞關(guān)于大腦和外面世界間的交流信息,，這樣就保證了大腦干細(xì)胞的定期儲(chǔ)備。因此如果我們不需要干細(xì)胞,，我們就不會(huì)將其用光,。（生物谷Bioon.com）
編譯自：Brain's Stem Cells 'Eavesdrop' to Find out When to Act
doi:10.1038/nature11306
PMC:
PMID:
Neuronal circuitry mechanism regulating adult quiescent neural stem-cell fate decision
Juan Song Chun Zhong Michael A. Bonaguidi Gerald J. Sun Derek Hsu Yan Gu Konstantinos Meletis Z. Josh Huang Shaoyu Ge Grigori Enikolopov Karl Deisseroth Bernhard Luscher Kimberly M. Christian Guo-li Ming Hongjun Song
Adult neurogenesis arises from neural stem cells within specialized niches1, 2, 3. Neuronal activity and experience, presumably acting on this local niche, regulate multiple stages of adult neurogenesis, from neural progenitor proliferation to new neuron maturation, synaptic integration and survival1, 3. It is unknown whether local neuronal circuitry has a direct impact on adult neural stem cells. Here we show that, in the adult mouse hippocampus, nestin-expressing radial glia-like quiescent neural stem cells4, 5, 6, 7, 8, 9 (RGLs) respond tonically to the neurotransmitter γ-aminobutyric acid (GABA) by means of γ2-subunit-containing GABAA receptors. Clonal analysis9 of individual RGLs revealed a rapid exit from quiescence and enhanced symmetrical self-renewal after conditional deletion of γ2. RGLs are in close proximity to terminals expressing 67-kDa glutamic acid decarboxylase (GAD67) of parvalbumin-expressing (PV+) interneurons and respond tonically to GABA released from these neurons. Functionally, optogenetic control of the activity of dentate PV+ interneurons, but not that of somatostatin-expressing or vasoactive intestinal polypeptide (VIP)-expressing interneurons, can dictate the RGL choice between quiescence and activation. Furthermore, PV+ interneuron activation restores RGL quiescence after social isolation, an experience that induces RGL activation and symmetrical division8. Our study identifies a niche cell–signal–receptor trio and a local circuitry mechanism that control the activation and self-renewal mode of quiescent adult neural stem cells in response to neuronal activity and experience.
