GABAergic activities enhance macrophage inflammatory protein-1α release from microglia (brain macrophages) in postnatal mouse brain
GABAergic activities enhance macrophage inflammatory protein-1α release from microglia (brain macrophages) in postnatal mouse brain
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DOI：
10.1113/jphysiol.2008.163923
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发表时间：
2009-02-15
影响因子：
5.5
通讯作者：
Kettenmann, Helmut
中科院分区：
文献类型：
--
作者：
Cheung, Giselle;Kann, Oliver;Kettenmann, Helmut
小胶质细胞（脑巨噬细胞）在胚胎和出生后早期发育期间侵入大脑，优先沿着纤维束迁移到最终位置，并从变形虫形态转变为分枝形态。入侵的小胶质细胞与其他脑细胞交流的信号在很大程度上是未知的。在这里，我们研究了出生后6至8日龄小鼠胼胝体中的变形虫小胶质细胞。这些细胞聚集在急性脑切片的表面。全细胞膜片钳记录显示，特定的GABA(A)受体激动剂muscimol触发了小胶质细胞内向内整流钾通道典型的瞬态电导增加。这种电流的增加不是由小胶质GABA(A)受体介导的，因为从切片表面移除的小胶质细胞不再反应，而培养的小胶质细胞只有在大脑切片靠近它们时才有反应。Muscimol触发脑切片细胞外钾浓度（[K+](o)）的短暂增加，实验中[K+](o)的升高模拟了Muscimol在小胶质细胞中的反应。此外，在成人脑切片中，muscimol仅导致[K+](o)增加一分钟，小胶质细胞对muscimol没有反应。反过来，[K+](o)的增加刺激了脑切片和小胶质细胞培养中趋化因子巨噬细胞炎症蛋白-1 α (mip1 - α)的释放，而星形胶质细胞则没有。我们的观察结果表明，在出生后发育早期，入侵的小胶质细胞通过感知[K+](o)的变化间接感知gaba能活动，从而导致mip1 - α释放增加。
Microglial cells (brain macrophages) invade the brain during embryonic and early postnatal development, migrate preferentially along fibre tracts to their final position and transform from an amoeboid to a ramified morphology. Signals by which the invading microglia communicate with other brain cells are largely unknown. Here, we studied amoeboid microglia in postnatal corpus callosum obtained from 6- to 8-day-old mice. These cells accumulated on the surface of acute brain slices. Whole-cell patch-clamp recordings revealed that the specific GABA(A) receptor agonist muscimol triggered a transient increase in conductance typical for inward rectifying potassium channels in microglia. This current increase was not mediated by microglial GABA(A) receptors since microglial cells removed from the slice surface no longer reacted and cultured microglia only responded when a brain slice was placed in their close vicinity. Muscimol triggered a transient increase in extracellular potassium concentration ([K+](o)) in brain slices and an experimental elevation of [K+](o) mimicked the muscimol response in microglial cells. Moreover, in adult brain slices, muscimol led only to a minute increase in [K+](o) and microglial cells failed to respond to muscimol. In turn, an increase in [K+](o) stimulated the release of chemokine macrophage inflammatory protein-1 alpha (MIP1-alpha) from brain slices and from cultures of microglia but not astrocytes. Our observations indicate that invading microglia in early postnatal development sense GABAergic activities indirectly via sensing changes in [K+](o) which results in an increase in MIP1-alpha release.