日本研究人員在最新一期《自然—神經(jīng)科學(xué)》雜志網(wǎng)絡(luò)版上發(fā)表論文說(shuō),,他們?cè)诶脤?shí)驗(yàn)鼠進(jìn)行的實(shí)驗(yàn)中,,發(fā)現(xiàn)一種小核糖核酸與腦神經(jīng)和視網(wǎng)膜神經(jīng)的形成有關(guān)。這是世界上首次發(fā)現(xiàn)小核糖核酸參與神經(jīng)線路的形成,,將有助于弄清癲癇和自閉癥等疾病的原因,。
小核糖核酸是一類不編碼制造蛋白質(zhì)的單鏈核糖核酸分子,主要參與控制基因表達(dá),。
日本大阪生物科學(xué)研究所,、名古屋大學(xué)和京都大學(xué)研究人員組成的聯(lián)合研究小組發(fā)現(xiàn),在腦內(nèi),,小核糖核酸-124a的含量很高,。于是他們培育了使腦內(nèi)小核糖核酸-124a不再發(fā)揮作用的實(shí)驗(yàn)鼠,并進(jìn)行分析,。結(jié)果發(fā)現(xiàn),,實(shí)驗(yàn)鼠的腦變小了,腦內(nèi)與記憶有關(guān)的海馬區(qū)的神經(jīng)細(xì)胞與通常情況下本不應(yīng)結(jié)合在一起的神經(jīng)細(xì)胞結(jié)合起來(lái),,神經(jīng)線路因此出現(xiàn)異常,。而在視網(wǎng)膜中,與視力和色覺(jué)有關(guān)的神經(jīng)細(xì)胞也死亡了,。
研究小組進(jìn)一步發(fā)現(xiàn),,在實(shí)驗(yàn)鼠腦發(fā)育過(guò)程中發(fā)揮作用、但應(yīng)隨著腦成熟而不再發(fā)揮作用的Lhx2基因在上述實(shí)驗(yàn)鼠的腦內(nèi)卻一直發(fā)揮作用,。研究小組認(rèn)為,,這是因小核糖核酸-124a不再發(fā)揮作用,使Lhx2基因不再受到遏制,,從而導(dǎo)致神經(jīng)異常,。(生物谷 Bioon.com)
doi:10.1038/nn.2897
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miR-124a is required for hippocampal axogenesis and retinal cone survival through Lhx2 suppression
Rikako Sanuki; Akishi Onishi; Chieko Koike; Rieko Muramatsu; Satoshi Watanabe; Yuki Muranishi; Shoichi Irie; Shinji Uneo; Toshiyuki Koyasu; Ryosuke Matsui; Yoan Chérasse; Yoshihiro Urade; Dai Watanabe; Mineo Kondo; Toshihide Yamashita; Takahisa Furukawa
MicroRNA-124a (miR-124a) is the most abundant microRNA expressed in the vertebrate CNS. Despite past investigations into the role of miR-124a, inconsistent results have left the in vivo function of miR-124a unclear. We examined the in vivo function of miR-124a by targeted disruption of Rncr3 (retinal non-coding RNA 3), the dominant source of miR-124a. Rncr3−/− mice exhibited abnormalities in the CNS, including small brain size, axonal mis-sprouting of dentate gyrus granule cells and retinal cone cell death. We found that Lhx2 is an in vivo target mRNA of miR-124a. We also observed that LHX2 downregulation by miR-124a is required for the prevention of apoptosis in the developing retina and proper axonal development of hippocampal neurons. These results suggest that miR-124a is essential for the maturation and survival of dentate gyrus neurons and retinal cones, as it represses Lhx2 translation.