首页> 外文期刊>Synapse >Cocaine Activates Homer1 Immediate Early Gene Transcription in the Mesocorticolimbic Circuit: Differential Regulation by Dopamine and Glutamate Signaling
【24h】

Cocaine Activates Homer1 Immediate Early Gene Transcription in the Mesocorticolimbic Circuit: Differential Regulation by Dopamine and Glutamate Signaling

机译:可卡因激活中皮层皮质回路中的Homer1立即早期基因转录:多巴胺和谷氨酸信号的差异调节。

获取原文
获取原文并翻译 | 示例
获取外文期刊封面目录资料

摘要

Homer proteins are intracellular scaffolding proteins that, among glutamate receptors, selectively bind to group1 metabotropic glutamate receptors and regulate their trafficking and intracellular signaling. Homer proteins have been implicated in synaptic and behavioral plasticity, including drug-seeking behavior after cocaine treatment. Homer1 gene activation leads to transcription of a variant mRNA (Homer1a), which functions as an immediate early gene. Homer1a competes with the constitutive Homer proteins (Homer1b/c/d, Homer2a/b, Homer3) for binding to group1 metabotropic glutamate and IP3 receptors. Binding of Homer1a to these proteins disrupts their association with the intracellular signaling scaffold and modulates receptor function. In this study, using RT-PCR, activation of Homer1a mRNA transcription in response to acute and repeated administration of cocaine was characterized in prefrontal cortex, nucleus accumbens, and ventral tegmental area, three mesocorticolimbic nuclei of the rat brain. Moreover, the dopaminergic and glutamatergic regulation of Homer1 gene activation by cocaine was investigated. Acute cocaine rapidly and transiently activated transcription of Homer1a mRNA in all three nuclei. However, repeated administration of cocaine was not effective in inducing the Homer1a mRNA transcription after various withdrawal times ranging from 2 h to 3 weeks. The acute cocaine-mediated activation of Homer1 gene was regulated by D1 but not D2 dopamine receptors. The blockade of AMPA or NMDA glutamate receptors did not prevent cocaine-mediated activation of Homer1 gene in the three mesocorticolimbic nuclei. These data indicate that acute administration of cocaine transiently activates Homer1 gene producing the immediate early gene Homer1a mRNA in the three mesocorticolimbic nuclei of the rat brain. Activation of Homer1 gene may contribute to the cocaine-mediated synaptic and behavioral plasticity.
机译:荷马蛋白是一种细胞内支架蛋白,在谷氨酸受体中可以选择性地与group1代谢型谷氨酸受体结合并调节其运输和细胞内信号传导。荷马蛋白与可卡因治疗后的突触和行为可塑性有关,包括寻药行为。 Homer1基因的激活导致变异mRNA(Homer1a)的转录,该mRNA作为立即的早期基因起作用。 Homer1a与组成型Homer蛋白(Homer1b / c / d,Homer2a / b,Homer3)竞争结合第1组代谢型谷氨酸和IP3受体。 Homer1a与这些蛋白质的结合破坏了它们与细胞内信号转导支架的结合并调节了受体的功能。在这项研究中,使用RT-PCR,在前额叶皮层,伏隔核和腹侧被盖区,大鼠脑的三个中皮层皮质核中表征了响应于可卡因的急性和重复给药而引起的Homer1a mRNA转录的激活。此外,研究了可卡因对Homer1基因激活的多巴胺能和谷氨酸能调节。急性可卡因迅速并短暂激活了所有三个核中的Homer1a mRNA转录。但是,重复服用可卡因在2 h至3周的各种停药时间后均无法有效诱导Homer1a mRNA转录。可卡因介导的Homer1基因的急性激活受D1而不是D2多巴胺受体的调节。 AMPA或NMDA谷氨酸受体的封锁并不能阻止可卡因介导的三个中皮层皮质核中Homer1基因的激活。这些数据表明,可卡因的急性给药会瞬时激活Homer1基因,从而在大鼠大脑的三个中皮层皮质核中立即产生早期基因Homer1a mRNA。 Homer1基因的激活可能有助于可卡因介导的突触和行为可塑性。

著录项

相似文献

  • 外文文献
  • 中文文献
  • 专利
获取原文

客服邮箱:kefu@zhangqiaokeyan.com

京公网安备:11010802029741号 ICP备案号:京ICP备15016152号-6 六维联合信息科技 (北京) 有限公司©版权所有
  • 客服微信

  • 服务号