科學(xué)家一直懷疑鐵沉積會(huì)導(dǎo)致神經(jīng)退化疾?。缗两鹕习Y等,但由于技術(shù)方面的缺陷,,鐵對(duì)于神經(jīng)的影響從未被觀察到過,。而最近,來自法國Bordeaux大學(xué)CNRS,、西班牙Sevilla大學(xué),、INSERM Grenoble神經(jīng)科學(xué)研究所和ESRF的科學(xué)家研究了體外產(chǎn)生多巴胺的神經(jīng)細(xì)胞中鐵的分布,。
多巴胺是哺乳動(dòng)物大腦神經(jīng)細(xì)胞間的化學(xué)信使。由于多巴胺和鐵能形成穩(wěn)定復(fù)合物,,來自Bordeaux的細(xì)胞化學(xué)成像小組的Richard Ortega認(rèn)為能通過緩沖多巴胺神經(jīng)元中的鐵產(chǎn)生一種保護(hù)作用,,而在帕金森氏癥中該系統(tǒng)可能存在問題。
為了測試以上假設(shè),,小組利用了歐洲同步加速輻射器發(fā)明的最新納米探針成像裝置,,來研究細(xì)胞中的元素分布。90納米的分辨率使得科學(xué)家可以觀察神經(jīng)傳遞素內(nèi)的元素分布,。納米探針通過聚焦強(qiáng)X射線激發(fā)樣品,,然后收集發(fā)射出的特征熒光。這能幫助區(qū)分一點(diǎn)上的不同微量元素,,然后通過點(diǎn)掃描得到細(xì)胞完整的多元素圖像,。
小組發(fā)現(xiàn)鐵儲(chǔ)存在神經(jīng)細(xì)胞中的多巴胺小泡中。這是鐵-多巴胺在小泡中共存的首個(gè)證據(jù),??茖W(xué)家同時(shí)發(fā)現(xiàn)當(dāng)多巴胺的制造發(fā)生困難時(shí),小泡中的鐵也快速降低,。這種多巴胺小泡在鐵儲(chǔ)存中的新作用對(duì)于了解帕金森氏癥等疾病的分子機(jī)制非常重要,。發(fā)生神經(jīng)異常時(shí),多巴胺小泡存儲(chǔ)被破壞,,最終將增加鐵-多巴胺復(fù)合物在神經(jīng)中的毒性,。結(jié)果發(fā)表在9月26日的PLoS ONE上。
除了研究神經(jīng)退化疾病外,,同步納米成像裝置還能用于其它需要分析鐵亞細(xì)胞分布的領(lǐng)域,,例如:金屬毒物學(xué)、化學(xué)致癌,、無機(jī)化合物的細(xì)胞藥理學(xué)等,。這也是科學(xué)家為何將結(jié)果公布于PLoS ONE這樣的開放性刊物的重要原因。ESRF的負(fù)責(zé)人Peter Cloetens說:“我們希望不同的研究組織知道這種儀器,,最好的方法是讓每個(gè)人都能知道研究結(jié)果,。” *(教育部科技發(fā)展中心)
原文鏈接:http://www.physorg.com/news111245716.html
原始出處:
PLoS ONE
Received: February 19, 2007; Accepted: August 8, 2007; Published: September 26, 2007
Iron Storage within Dopamine Neurovesicles Revealed by Chemical Nano-Imaging
Richard Ortega1*, Peter Cloetens2, Guillaume Devès1, Asunción Carmona3, Sylvain Bohic4
1 Cellular Chemical Imaging and Speciation Group, Chimie Nucléaire Analytique Bioenvironnementale, Centre National de la Recherche Scientifique, Université Bordeaux 1, Gradignan, France, 2 X-Ray Imaging Group, European Synchrotron Radiation Facility, Grenoble, France, 3 Centro Nacional de Aceleradores, Universidad de Sevilla, Sevilla, Spain, 4 INSERM U-836, Equipe Rayonnement Synchrotron et Recherche Médicale, Grenoble Institut des Neurosciences, European Synchrotron Radiation Facility, Grenoble, France
Abstract
Altered homeostasis of metal ions is suspected to play a critical role in neurodegeneration. However, the lack of analytical technique with sufficient spatial resolution prevents the investigation of metals distribution in neurons. An original experimental setup was developed to perform chemical element imaging with a 90 nm spatial resolution using synchrotron-based X-ray fluorescence. This unique spatial resolution, combined to a high brightness, enables chemical element imaging in subcellular compartments. We investigated the distribution of iron in dopamine producing neurons because iron-dopamine compounds are suspected to be formed but have yet never been observed in cells. The study shows that iron accumulates into dopamine neurovesicles. In addition, the inhibition of dopamine synthesis results in a decreased vesicular storage of iron. These results indicate a new physiological role for dopamine in iron buffering within normal dopamine producing cells. This system could be at fault in Parkinson's disease which is characterized by an increased level of iron in the substancia nigra pars compacta and an impaired storage of dopamine due to the disruption of vesicular trafficking. The re-distribution of highly reactive dopamine-iron complexes outside neurovesicles would result in an enhanced death of dopaminergic neurons.