Conditional Knockout of mGluR5 From Astrocytes During Epilepsy Development Impairs High-Frequency Glutamate Uptake Umpierre AD, West PJ, White JA, et al. J Neurosci. 2019;39(4):727-742. doi:10.1523/JNEUROSCI.1148-18.2018 Astrocyte expression of metabotropic glutamate receptor 5 (mGluR5) is consistently observed in resected tissue from patients with epilepsy and is equally prevalent in animal models of epilepsy. However, little is known about the functional signaling properties or downstream consequences of astrocyte mGluR5 activation during epilepsy development. In the rodent brain, astrocyte mGluR5 expression is developmentally regulated and confined in expression/function to the first weeks of life, with similar observations made in human control tissue. Herein, we demonstrate that mGluR5 expression and function dramatically increase in a mouse model of temporal lobe epilepsy. Interestingly, in both male and female mice, mGluR5 function persists in the astrocyte throughout the process of epileptogenesis following status epilepticus. However, mGluR5 expression and function are transient in animals that do not develop epilepsy over an equivalent time period, suggesting that patterns of mGluR5expression may signify continuing epilepsy development or its resolution. We demonstrate that, during epileptogenesis, astrocytes reacquire mGluR5-dependent calcium transients following agonist application or synaptic glutamate release, a feature of astrocyte-neuron communication absent since early development. Finally, we find that the selective and conditional knockout of mGluR5 signaling from astrocytes during epilepsy development slows the rate of glutamate clearance through astrocyte glutamate transporters under high-frequency stimulation conditions, a feature that suggests astrocyte mGluR5 expression during epileptogenesis may recapitulate earlier developmental roles in regulating glutamate transporter function.

中文翻译：

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星形胶质细胞受体重生。

癫痫发展期间星形胶质细胞中 mGluR5 的条件性敲除会损害高频谷氨酸摄取 Umpierre AD、West PJ、White JA 等。J 神经科学。2019;39(4):727-742。doi:10.1523/JNEUROSCI.1148-18.2018 代谢型谷氨酸受体 5 (mGluR5) 的星形胶质细胞表达在癫痫患者的切除组织中持续观察到，并且在癫痫动物模型中同样普遍。然而，对于癫痫发展过程中星形胶质细胞 mGluR5 激活的功能信号特性或下游后果知之甚少。在啮齿动物的大脑中，星形胶质细胞 mGluR5 的表达在发育上受到调节，并且在生命的最初几周内表达/功能受限，在人类对照组织中也有类似的观察结果。在此处，我们证明 mGluR5 表达和功能在颞叶癫痫小鼠模型中显着增加。有趣的是，在雄性和雌性小鼠中，在癫痫持续状态后的整个癫痫发生过程中，mGluR5 功能在星形胶质细胞中持续存在。然而，mGluR5 的表达和功能在同等时间段内未发生癫痫的动物中是短暂的，这表明 mGluR5 表达的模式可能意味着癫痫的持续发展或其消退。我们证明，在癫痫发生过程中，星形胶质细胞在应用激动剂或突触谷氨酸盐释放后重新获得依赖于 mGluR5 的钙瞬变，这是自早期发育以来星形胶质细胞-神经元通信的一个特征。最后，