Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission.
Microglial morphology and dynamic behavior is regulated by ionotropic glutamatergic and GABAergic neurotransmission.
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小胶质细胞形态和动态行为受离子型谷氨酸能和GABA能神经传递的调节。
DOI：
10.1371/journal.pone.0015973
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发表时间：
2011-01-25
期刊：
影响因子：
3.7
通讯作者：
Wong WT
中科院分区：
文献类型：
--
作者：
Fontainhas AM;Wang M;Liang KJ;Chen S;Mettu P;Damani M;Fariss RN;Li W;Wong WT
小胶质细胞是中枢神经系统的主要常驻免疫细胞，与神经退行性疾病的病理有关。在基础或“休息”条件下，小胶质细胞具有分支形态，并在其过程中表现出动态的测量运动。尽管这一现象很突出，但小胶质细胞形态和动态行为的功能和调控尚不完全清楚。我们在这里研究神经传递是否以及如何调节“静息”小胶质细胞的形态和行为。我们采用了一个离体小鼠视网膜移植系统，其中内源性神经传递和动态小胶质细胞行为存在。我们利用活细胞延时共聚焦成像技术研究了gfp标记的视网膜小胶质细胞对神经递质激动剂和拮抗剂的形态学和行为。膜片钳电生理和谷氨酸受体的免疫组织化学定位也被用来研究小胶质细胞对神经传递的直接与间接影响。视网膜小胶质细胞的形态和动态行为不是细胞自主调节的，而是由内源性神经传递调节的。形态学参数和过程运动受不同神经传递方式的差异调节，嗜离子性谷氨酸能神经传递增加，嗜离子性氨基丁酸能神经传递降低。然而，这些神经递质对视网膜小胶质细胞的影响不太可能直接介导；局部应用神经递质不能引起小胶质细胞膜片钳记录的电反应，免疫荧光标记的嗜离子性谷氨酸能受体不能定位在小胶质细胞体或突起上。相反，这些影响是通过细胞外ATP间接介导的，ATP在响应谷氨酸能神经传递时通过丙戊酸敏感的泛联蛋白半通道释放。我们的研究结果表明，神经传递在调节视网膜“静息”小胶质细胞的形态和行为中起内源性作用。这些发现说明了中枢神经系统的神经和免疫区室之间的组成信号模式，通过这种模式，免疫细胞可能与神经活动水平一致受到调节。
Microglia represent the primary resident immune cells in the CNS, and have been implicated in the pathology of neurodegenerative diseases. Under basal or “resting” conditions, microglia possess ramified morphologies and exhibit dynamic surveying movements in their processes. Despite the prominence of this phenomenon, the function and regulation of microglial morphology and dynamic behavior are incompletely understood. We investigate here whether and how neurotransmission regulates “resting” microglial morphology and behavior. We employed an ex vivo mouse retinal explant system in which endogenous neurotransmission and dynamic microglial behavior are present. We utilized live-cell time-lapse confocal imaging to study the morphology and behavior of GFP-labeled retinal microglia in response to neurotransmitter agonists and antagonists. Patch clamp electrophysiology and immunohistochemical localization of glutamate receptors were also used to investigate direct-versus-indirect effects of neurotransmission by microglia. Retinal microglial morphology and dynamic behavior were not cell-autonomously regulated but are instead modulated by endogenous neurotransmission. Morphological parameters and process motility were differentially regulated by different modes of neurotransmission and were increased by ionotropic glutamatergic neurotransmission and decreased by ionotropic GABAergic neurotransmission. These neurotransmitter influences on retinal microglia were however unlikely to be directly mediated; local applications of neurotransmitters were unable to elicit electrical responses on microglia patch-clamp recordings and ionotropic glutamatergic receptors were not located on microglial cell bodies or processes by immunofluorescent labeling. Instead, these influences were mediated indirectly via extracellular ATP, released in response to glutamatergic neurotransmission through probenecid-sensitive pannexin hemichannels. Our results demonstrate that neurotransmission plays an endogenous role in regulating the morphology and behavior of “resting” microglia in the retina. These findings illustrate a mode of constitutive signaling between the neural and immune compartments of the CNS through which immune cells may be regulated in concert with levels of neural activity.
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影响因子：
5.3
作者：
Jung, S;Aliberti, J;Littman, DR
通讯作者：
Littman, DR
DOI：
10.1523/jneurosci.0055-10.2010
发表时间：
2010-03-17
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
Kawamura M Jr;Ruskin DN;Masino SA
通讯作者：
Masino SA
影响因子：
3.3
作者：
LAWSON, LJ;PERRY, VH;GORDON, S
通讯作者：
GORDON, S
DOI：
10.1073/pnas.0611280104
发表时间：
2007-04-10
影响因子：
11.1
作者：
Huang, Yi-Jen;Maruyama, Yutaka;Roper, Stephen D.
通讯作者：
Roper, Stephen D.
DOI：
10.1124/jpet.108.146365
发表时间：
2009-02-01
影响因子：
3.5
作者：
Ma, Weihong;Hui, Hui;Surprenant, Annmarie
通讯作者：
Surprenant, Annmarie