動(dòng)物大腦中的小膠質(zhì)細(xì)胞具有修復(fù)受損腦組織的特殊功能,,它們被稱為“腦內(nèi)醫(yī)生”,。日本研究人員最近借助一種特殊的顯微鏡,首次觀察到了這些“醫(yī)生”的工作狀態(tài),。
日本自然科學(xué)研究機(jī)構(gòu)的研究人員4月1日在《神經(jīng)科學(xué)雜志》(The Journal of Neuroscience )網(wǎng)絡(luò)版上發(fā)表文章介紹說(shuō),,小膠質(zhì)細(xì)胞具備免疫功能,它們能修復(fù)因腦中風(fēng)或腦血管堵塞而受損的腦組織或清除腦內(nèi)的“廢物”,。但是,,小膠質(zhì)細(xì)胞是如何在人類和其他動(dòng)物的腦內(nèi)檢查神經(jīng)、履行醫(yī)生職責(zé)的,,之前一直無(wú)人知曉,。在本次研究中,研究人員利用經(jīng)改良的雙光子激光顯微鏡,,首次成功進(jìn)行了腦內(nèi)實(shí)況攝影,。
研究人員觀察到,小膠質(zhì)細(xì)胞以頻繁的日常檢查和“觸診”的方式來(lái)扮演醫(yī)生的角色,。通常情況下,,小膠質(zhì)細(xì)胞會(huì)毫不懈怠地對(duì)腦神經(jīng)細(xì)胞之間相互接觸的部位——突觸進(jìn)行健康檢查。檢查的頻率大約為一小時(shí)一次,,一次持續(xù)5分鐘,。如果神經(jīng)活動(dòng)增加,,檢查次數(shù)也會(huì)相應(yīng)增加。而一旦腦組織受到傷害,,小膠質(zhì)細(xì)胞會(huì)持續(xù)一個(gè)小時(shí)以上將整個(gè)突觸包裹起來(lái),,如同觸摸著突觸進(jìn)行精密檢查。
研究人員預(yù)測(cè),,在腦神經(jīng)細(xì)胞受到傷害恢復(fù)的過(guò)程中,,或者是在腦的發(fā)育階段,小膠質(zhì)細(xì)胞的這種健康檢查和精密檢查作用巨大,。他們認(rèn)為,,利用本次發(fā)現(xiàn)的機(jī)制,借助藥物或生物活性因子刺激受損腦組織中的小膠質(zhì)細(xì)胞,,或許能夠加快腦的修復(fù),,或者使腦功能恢復(fù)訓(xùn)練更加有效。(生物谷Bioon.com)
生物谷推薦原始出處:
The Journal of Neuroscience, April 1, 2009, 29(13):3974-3980; doi:10.1523/JNEUROSCI.4363-08.2009
Resting Microglia Directly Monitor the Functional State of Synapses In Vivo and Determine the Fate of Ischemic Terminals
Hiroaki Wake,1,2 Andrew J. Moorhouse,1,3 Shozo Jinno,4 Shinichi Kohsaka,5 and Junichi Nabekura1,2,6
1Division of Homeostatic Development, National Institute of Physiological Sciences, Okazaki 444-8585, Japan, 2Core Research for Evolutional Science and Technology, Japan Science and Technology Agency, Saitama 332-0012, Japan, 3Membrane Biophysics Laboratory, School of Medical Sciences, The University of New South Wales, Sydney 2052, Australia, 4Department of Anatomy and Neurobiology, Graduate School of Medical Sciences, Kyushu University, Fukuoka 812-8582, Japan, 5Department of Neurochemistry, National Institute of Neuroscience, Kodaira, Tokyo 187-8502, Japan, and 6Department of Physiological Sciences, The Graduate School for Advanced Study (Sokendai), Hayama 240-0198, Japan
Recent studies have identified the important contribution of glial cells to the plasticity of neuronal circuits. Resting microglia, the primary immune effector cells in the brain, dynamically extend and retract their processes as if actively surveying the microenvironment. However, just what is being sampled by these resting microglial processes has not been demonstrated in vivo, and the nature and function of any interactions between microglia and neuronal circuits is incompletely understood. Using in vivo two-photon imaging of fluorescent-labeled neurons and microglia, we demonstrate that the resting microglial processes make brief (5 min) and direct contacts with neuronal synapses at a frequency of about once per hour. These contacts are activity-dependent, being reduced in frequency by reductions in neuronal activity. After transient cerebral ischemia, the duration of these microglia–synapse contacts are markedly prolonged (1 h) and are frequently followed by the disappearance of the presynaptic bouton. Our results demonstrate that at least part of the dynamic motility of resting microglial processes in vivo is directed toward synapses and propose that microglia vigilantly monitor and respond to the functional status of synapses. Furthermore, the striking finding that some synapses in the ischemic areas disappear after prolonged microglial contact suggests microglia contribute to the subsequent increased turnover of synaptic connections. Further understanding of the mechanisms involved in the microglial detection of the functional state of synapses, and of their role in remodeling neuronal circuits disrupted by ischemia, may lead to novel therapies for treating brain injury that target microglia.