CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion
CXCR3-dependent microglial recruitment is essential for dendrite loss after brain lesion
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DOI：
10.1523/jneurosci.2451-04.2004
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发表时间：
2004-09-29
影响因子：
5.3
通讯作者：
Kettenmann, H
中科院分区：
文献类型：
--
作者：
Rappert, A;Bechmann, I;Kettenmann, H
小胶质细胞是CNS的常驻巨噬细胞群体，被认为是其主要的免疫活性成分。它们被任何类型的大脑病理激活，并可迁移到病变部位。趋化因子CXCL10在神经元中表达以响应脑损伤，并且是激活小胶质细胞并将其引导至损伤部位的信号候选物。我们最近在小胶质细胞中鉴定了CXCL10的相应受体CXCR3，并证明该受体系统控制小胶质细胞迁移。我们现在已经测试了CXCR3信号对内嗅皮层损伤后细胞反应的影响。在野生型小鼠中，小胶质细胞在损伤后的前3天内迁移到轴突变性区，其中损伤后8天失神经支配的中间神经元树突随后丢失。相反，CXCR3基因敲除小鼠中小胶质细胞的募集受损，并且引人注目的是，去神经支配的远端树突在轴突变性区中得以维持。作为评估小胶质细胞增殖的损伤模型，在面神经轴突切断术后未观察到野生型和基因敲除小鼠之间的差异。这表明CXCR3信号传导在小胶质细胞募集中至关重要，而不是增殖，并且这种募集是神经元重组的基本要素。
Microglia are the resident macrophage population of the CNS and are considered its major immunocompetent elements. They are activated by any type of brain pathology and can migrate to the lesion site. The chemokine CXCL10 is expressed in neurons in response to brain injury and is a signaling candidate for activating microglia and directing them to the lesion site. We recently identified CXCR3, the corresponding receptor for CXCL10, in microglia and demonstrated that this receptor system controls microglial migration. We have now tested the impact of CXCR3 signaling on cellular responses after entorhinal cortex lesion. In wild-type mice, microglia migrate within the first 3 d after lesion into the zone of axonal degeneration, where 8 d after lesion denervated dendrites of interneurons are subsequently lost. In contrast, the recruitment of microglia was impaired in CXCR3 knock-out mice, and, strikingly, denervated distal dendrites were maintained in zones of axonal degeneration. No differences between wild-type and knock-out mice were observed after facial nerve axotomy, as a lesion model for assessing microglial proliferation. This shows that CXCR3 signaling is crucial in microglia recruitment but not proliferation, and this recruitment is an essential element for neuronal reorganization.