日本研究人員在最新一期《自然—神經(jīng)科學》雜志網(wǎng)絡版上發(fā)表論文說,,他們在利用實驗鼠進行的實驗中,,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。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,。
日本大阪生物科學研究所,、名古屋大學和京都大學研究人員組成的聯(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)揮作用的實驗鼠,并進行分析,。結果發(fā)現(xiàn),,實驗鼠的腦變小了,腦內(nèi)與記憶有關的海馬區(qū)的神經(jīng)細胞與通常情況下本不應結合在一起的神經(jīng)細胞結合起來,,神經(jīng)線路因此出現(xiàn)異常,。而在視網(wǎng)膜中,與視力和色覺有關的神經(jīng)細胞也死亡了,。
研究小組進一步發(fā)現(xiàn),,在實驗鼠腦發(fā)育過程中發(fā)揮作用、但應隨著腦成熟而不再發(fā)揮作用的Lhx2基因在上述實驗鼠的腦內(nèi)卻一直發(fā)揮作用,。研究小組認為,,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.