人蛙混合卵子或許能揭開(kāi)孤獨(dú)病神經(jīng)學(xué)上的奧秘,。為了證實(shí)這一點(diǎn),,科學(xué)家利用已故孤獨(dú)癥患者保存好的大腦細(xì)胞和非洲食肉蛙――光滑爪蟾(Xenopus)的卵子結(jié)合起來(lái),培育人蛙混合卵子,,以探查孤獨(dú)癥患者大腦細(xì)胞的行為,。
光滑爪蟾的卵子運(yùn)作方式有點(diǎn)像人類(lèi)的神經(jīng)元。因此,,此混合細(xì)胞可以充當(dāng)孤獨(dú)癥患者的活大腦,。開(kāi)發(fā)此研究辦法的美國(guó)加州大學(xué)神經(jīng)生物學(xué)家里卡多·米勒迪說(shuō):“這簡(jiǎn)直就像你在研究人類(lèi)大腦中的神經(jīng)元。”
米勒迪先前用光滑爪蟾的卵子研究過(guò)癲癇癥,,結(jié)果表明癲癇癥患者的一些大腦細(xì)胞在感知某種分子的行動(dòng)時(shí)有麻煩,,而這種分子是幫助封閉神經(jīng)細(xì)胞活動(dòng)的。這種有麻煩的蛋白質(zhì)叫“神經(jīng)傳遞素受體”,,是感知通信神經(jīng)元化學(xué)信號(hào)的,。
一些研究人員認(rèn)為孤獨(dú)癥是由鏡像神經(jīng)元功能故障導(dǎo)致的,因?yàn)殓R像神經(jīng)元在理解他人行為方面具有重要作用,,因此,,鏡像神經(jīng)元功能故障將導(dǎo)致癲癇癥和其它癥狀,。
光滑爪蟾胚胎發(fā)育過(guò)程
為了解孤獨(dú)癥患者的神經(jīng)傳遞素信號(hào)傳輸是否出現(xiàn)異常,米勒迪小組從年齡在8-39歲的6名已故孤獨(dú)癥患者采集了大腦樣本,,將含有神經(jīng)傳遞素受體的細(xì)胞膜和光滑爪蟾的卵子膜結(jié)合在一起,。與此同時(shí),他們將沒(méi)有任何精神病歷史的患者的大腦細(xì)胞也與光滑爪蟾的卵子結(jié)合,,以作對(duì)照,。之后,米勒迪小組將此混合卵子浸沒(méi)在神經(jīng)傳遞素化學(xué)物中,,測(cè)量每一個(gè)卵子所產(chǎn)生的電壓,。由于光滑爪蟾的卵子不能應(yīng)答神經(jīng)傳遞素,因此,,人類(lèi)蛋白質(zhì)完全負(fù)責(zé)任何電流的產(chǎn)生,。
結(jié)果發(fā)現(xiàn)6名已故孤獨(dú)癥患者中的4名患者的大腦對(duì)神經(jīng)傳遞素化學(xué)物的應(yīng)答能力均小于對(duì)照組。米勒迪小組將他們的研究成果發(fā)表在最新出版的美國(guó)《國(guó)家科學(xué)院院刊》(PNAS)上,。不過(guò),,米勒迪表示還需更多的研究來(lái)證實(shí)這一結(jié)論。他說(shuō):“孤獨(dú)癥是一種非常廣泛的疾病,,有不同的起因和不同的問(wèn)題,。”
美國(guó)馬里蘭州巴爾的摩肯尼迪-克雷格學(xué)院(Kennedy-Krieger Institute)的神經(jīng)生物學(xué)家喬納森·裴夫斯勒認(rèn)可蛙卵用于研究某些類(lèi)型的孤獨(dú)癥,或許能找到新的治療辦法,。他表示其它精神疾病如抑郁癥和帕金森癥能通過(guò)調(diào)節(jié)神經(jīng)傳遞素的活動(dòng)性來(lái)加以治療,。混合蛙卵或許也能暗示神經(jīng)傳遞素存在功能故障,。(生物谷Bioon.com)
生物谷推薦原始出處:
PNAS,,doi: 10.1073/pnas.0804386105,Agenor Limon,,Ricardo Miledi
Microtransplantation of neurotransmitter receptors from postmortem autistic brains to Xenopus oocytes
Agenor Limon*, Jorge Mauricio Reyes-Ruiz*, and Ricardo Miledi*,†,‡
+Author Affiliations
*Department of Neurobiology and Behavior, University of California, Irvine, CA 92697-4550 and
†Instituto de Neurobiología, Universidad Nacional Autónoma de México, Campus Juriquilla, Boulevard Juriquilla 3001, 76230 Juriquilla, Querétaro, México
Contributed by Ricardo Miledi, University of California, Irvine, CA, May 10, 2008 (sent for review April 11, 2008)
Abstract
Autism is a complex disorder that arises from the pervasive action of genetic and epigenetic factors that alter synaptic connectivity of the brain. Although GABA and glutamate receptors seem to be two of those factors, very little is known about the functional properties of the autistic receptors. Autistic tissue samples stored in brain banks usually have relatively long postmortem times, and it is highly desirable to know whether neurotransmitter receptors in such tissues are still functional. Here we demonstrate that native receptors microtransplanted from autistic brains, as well as de novo mRNA-expressed receptors, are still functional and susceptible to detailed electrophysiological characterization even after long postmortem intervals. The opportunity to study the properties of human receptors present in diseased brains not only opens new avenues toward understanding autism and other neurological disorders, but it also makes the microtransplantation method a useful translational system to evaluate and develop novel medicinal drugs.