Down-regulation of GluK2 kainate receptor expression by chronic treatment with mood-stabilizing anti-convulsants or lithium in cultured astrocytes and brain, but not in neurons
Down-regulation of GluK2 kainate receptor expression by chronic treatment with mood-stabilizing anti-convulsants or lithium in cultured astrocytes and brain, but not in neurons
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在培养的星形胶质细胞和大脑中，长期使用稳定情绪的抗惊厥药或锂治疗，可下调 GluK2 红藻氨酸受体的表达，但在神经元中则不然。
DOI：
10.1016/j.neuropharm.2009.07.004
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发表时间：
2009-09-01
影响因子：
4.7
通讯作者：
Peng, Liang
中科院分区：
文献类型：
--
作者：
Li, Baoman;Zhang, Shiquen;Peng, Liang
最近的研究表明，双相情感障碍中谷氨酸能的传递可能被改变，并受到长期使用情绪稳定药物治疗的影响。Kainate受体可能特别感兴趣，因为i)它们在突触传递、长期增强（LTP）和长期抑制（LDP）中具有调节作用；ii) Kainate受体亚基GluK2 （GluR6）参与被认为是躁狂症特征的行为症状，已经在敲除小鼠中得到证实。谷氨酸受体不仅在神经元上表达，而且在星形胶质细胞上表达，在那里它们有助于调节突触活动。我们之前的研究表明，小鼠星形胶质细胞原代培养物对治疗相关浓度的任何“经典”情绪稳定药物（锂离子（Li+）、卡马西平或丙戊酸盐）的慢性而非急性治疗有反应，其肌醇摄取、cPLA(2)表达和细胞内ph值发生变化。在目前的工作中，我们发现i)在小鼠星形胶质细胞原代培养物和体内大脑中，kainate受体家族的GluK2亚基基因表达相似；ii)卡马西平慢性治疗后，星形胶质细胞和大脑中GluK2 mRNA和蛋白表达降低，但对神经元无影响；iii)奥卡马西平、丙戊酸、Li+对星形胶质细胞的下调作用相似，均具有情绪稳定作用，而抗惊厥药物托吡酯则无此作用；iv)用上述任何一种情绪稳定药物慢性治疗后，在培养的星形胶质细胞中正常发生的谷氨酸诱导的ERK磷酸化被消除。讨论了这些效应与先前证明的效应之间可能的关系。2009爱思唯尔有限公司版权所有。
Recent studies have indicated that glutamatergic transmission may be altered in bipolar disorder and affected by chronic treatment with mood-stabilizing drugs. Kainate receptors may be of special interest because i) they have a modulatory role in synaptic transmission, long-term potentiation (LTP) and long-term depression (LDP): and ii) involvement of the kainate receptor subunit GluK2 (GluR6) in behavioral symptoms thought characteristic of mania has been demonstrated in knock-out mice. Glutamate receptors are expressed not only on neurons, but also on astrocytes, where they contribute to regulation of synaptic activity. We have previously shown that primary cultures of mouse astrocytes respond to chronic but not acute treatment with therapeutic relevant concentrations of any of the 'classical' moodstabilizing drugs, lithium ion (Li+), carbamazepine or valproate, with changes in uptake of myo-inositol, cPLA(2) expression and intracellular pH. In the present work, we found i) similar gene expression of the GluK2 subunit of the kainate receptor family in primary cultures of mouse astrocytes and in brain in vivo; ii) a reduction of mRNA and protein expression of GluK2 in astrocytes and in brain after chronic treatment with carbamazepine but no effect in neurons; iii) similar down-regulation in astrocytes by oxcarbamazepine, valproic acid or Li+, which all have mood-stabilizing effect, but not by the anti-convulsant topiramate, which has no such activity; and iv) abrogation of a normally occurring glutamate-induced ERK phosphorylation in the cultured astrocytes after chronic treatment with any of the mood-stabilizing drugs mentioned above. Possible relationships between these and previously demonstrated effects are discussed. (C) 2009 Elsevier Ltd. All rights reserved.