动物大脑中的小胶质细胞具有修复受损脑组织的特殊功能,它们被称为“脑内医生”。日本研究人员最近借助一种特殊的显微镜,首次观察到了这些“医生”的工作状态。
日本自然科学研究机构的研究人员4月1日在《神经科学杂志》(The Journal of Neuroscience )网络版上发表文章介绍说,小胶质细胞具备免疫功能,它们能修复因脑中风或脑血管堵塞而受损的脑组织或清除脑内的“废物”。但是,小胶质细胞是如何在人类和其他动物的脑内检查神经、履行医生职责的,之前一直无人知晓。在本次研究中,研究人员利用经改良的双光子激光显微镜,首次成功进行了脑内实况摄影。
研究人员观察到,小胶质细胞以频繁的日常检查和“触诊”的方式来扮演医生的角色。通常情况下,小胶质细胞会毫不懈怠地对脑神经细胞之间相互接触的部位——突触进行健康检查。检查的频率大约为一小时一次,一次持续5分钟。如果神经活动增加,检查次数也会相应增加。而一旦脑组织受到伤害,小胶质细胞会持续一个小时以上将整个突触包裹起来,如同触摸着突触进行精密检查。
研究人员预测,在脑神经细胞受到伤害恢复的过程中,或者是在脑的发育阶段,小胶质细胞的这种健康检查和精密检查作用巨大。他们认为,利用本次发现的机制,借助药物或生物活性因子刺激受损脑组织中的小胶质细胞,或许能够加快脑的修复,或者使脑功能恢复训练更加有效。(生物谷Bioon.com)
生物谷推荐原始出处:
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.