Status epilepticus induces a particular microglial activation state characterized by enhanced purinergic signaling
Status epilepticus induces a particular microglial activation state characterized by enhanced purinergic signaling
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DOI：
10.1523/jneurosci.1820-08.2008
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发表时间：
2008-09-10
影响因子：
5.3
通讯作者：
Audinat, Etienne
中科院分区：
文献类型：
--
作者：
Avignone, Elena;Ulmann, Lauriane;Audinat, Etienne
小胶质细胞是CNS的常驻巨噬细胞，并且它们的活化在与许多脑疾病（包括缺血、阿尔茨海默病和帕金森病以及癫痫）相关的炎症反应中起关键作用。然而，小胶质细胞功能特性在癫痫中的变化却很少被研究。在这里，我们使用了一个模型的癫痫持续状态（SE）诱导的腹膜内注射红藻氨酸的特点，在CX 3CR 1（eGFP/+）小鼠海马切片中的小胶质细胞的特性。SE在3小时内诱导海马中炎症介质的表达增加，随后是小胶质细胞形态的改变、小胶质细胞增殖和CA 1中显著的神经变性。在SE后24-48 h检测到海马小胶质细胞电生理固有膜特性的变化，特别是新的电压激活钾电流的出现。与海马中嘌呤能受体mRNA上调的观察结果一致，我们还提供了药理学证据，表明SE后48 h，由P2受体（包括P2 X（7）、P2 Y（6）和P2 Y（12））激活介导的小胶质细胞膜电流增加。作为嘌呤能信号的这种改变的功能结果，癫痫海马中小胶质细胞向P2 Y（12）受体激动剂来源的运动速度是其两倍。这项研究是第一次在体内炎症模型中对小胶质细胞激活的功能描述，并为癫痫持续状态后存在特定的小胶质细胞激活状态提供了证据。
Microglia cells are the resident macrophages of the CNS, and their activation plays a critical role in inflammatory reactions associated with many brain disorders, including ischemia, Alzheimer's and Parkinson's diseases, and epilepsy. However, the changes of microglia functional properties in epilepsy have rarely been studied. Here, we used a model of status epilepticus ( SE) induced by intraperitoneal kainate injections to characterize the properties of microglial cells in hippocampal slices from CX3CR1(eGFP/+) mice. SE induced within 3 h an increased expression of inflammatory mediators in the hippocampus, followed by a modification of microglia morphology, a microglia proliferation, and a significant neurodegeneration in CA1. Changes in electrophysiological intrinsic membrane properties of hippocampal microglia were detected at 24-48 h after SE with, in particular, the appearance of new voltage-activated potassium currents. Consistent with the observation of an upregulation of purinergic receptor mRNAs in the hippocampus, we also provide pharmacological evidence that microglia membrane currents mediated by the activation of P2 receptors, including P2X(7), P2Y(6), and P2Y(12), were increased 48 h after SE. As a functional consequence of this modification of purinergic signaling, motility of microglia processes toward a source of P2Y(12) receptor agonist was twice as fast in the epileptic hippocampus. This study is the first functional description of microglia activation in an in vivo model of inflammation and provides evidence for the existence of a particular microglial activation state after a status epilepticus.