Involvement of the brain metabotropic glutamate receptor ^subtypes 5 and 7 in chronic psychosocial stress

大脑代谢型谷氨酸受体^亚型 5 和 7 参与慢性心理社会压力

• 批准号: 196351799
• 负责人: Professor Dr. Peter Josef Flor
• 金额: --
• 依托单位: Institut für Zoologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2010
• 资助国家: 德国
• 起止时间: 2009-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/196351799?language=en
• 关键词: Involvement; brain; metabotropic; glutamate; receptor

The role of the brain metabotropic glutamate receptor (mGluR) subtypes mGluR5 and mGluR7 in anxiety- and acute stress-related behaviours and physiology in rodents is well established, tn contrast, virtually nothing is known about their involvement in chronic stress. Here we intend to determine the effects of genetic ablation and local knock-down, as well as pharmacological modulation of mGluRS and mGtuR7 on behavioural and physiological consequences of chronic psychosocial stress in mice using the established chronic subordinate colony housing (CSC) paradigm. Also, we want to assess more broadly the effects of CSC on the mGluR system of the brain. Thus, quantitative PCR will be used to determine CSC-induced changes of mGluRl-8 and their intracellular regulatory proteins. Further, groups of knock-out mice of mGluRS, of mGluR7, and corresponding wild-types exposed to CSC will be assessed with respect to selected stress-related behavioural parameters, neuronal and hormonal HPA-axis responsiveness, selected brain mRNA levels, as well as immune functions. Moreover, selective pharmacological agents for mGluRS and mGtuR7 will be utilized to investigate their effects on the consequences of CSC and for comparison with the genetic knock-outs. Finally, local siRNA-mediated knock-down and overexpression of mGluRs, mediated by adeno-associated viral vectors, wilt further define the criticat involvement of the receptors in specific brain regions and will assist to dissect and suggest which mode and direction of mGluR subtype-modulation could be most beneficial for future therapeutic intervention in human disorders related to chronic psychosocial stress.

大脑代谢型谷氨酸受体 (mGluR) 亚型 mGluR5 和 mGluR7 在啮齿类动物焦虑和急性应激相关行为和生理学中的作用已得到充分证实，但相比之下，人们对它们与慢性应激的参与几乎一无所知。在这里，我们打算使用已建立的慢性从属群体居住（CSC）范例来确定基因消融和局部敲除以及 mGluRS 和 mGtuR7 的药理调节对小鼠慢性心理社会应激的行为和生理后果的影响。此外，我们希望更广泛地评估 CSC 对大脑 mGluR 系统的影响。因此，定量PCR将用于确定CSC诱导的mGluR1-8及其细胞内调节蛋白的变化。此外，将评估暴露于 CSC 的 mGluRS、mGluR7 和相应野生型小鼠的选定应激相关行为参数、神经元和激素 HPA 轴反应性、选定脑 mRNA 水平以及免疫功能。此外，mGluRS 和 mGtuR7 的选择性药物将用于研究它们对 CSC 后果的影响，并与基因敲除进行比较。最后，由腺相关病毒载体介导的局部 siRNA 介导的 mGluR 敲低和过度表达，将进一步明确受体在特定大脑区域的关键参与，并将有助于剖析和建议 mGluR 亚型调节的哪种模式和方向可能最有利于未来对与慢性心理社会压力相关的人类疾病的治疗干预。

项目成果

Blocking metabotropic glutamate receptor subtype 5 relieves maladaptive chronic stress consequences

• DOI: 10.1016/j.bbi.2016.08.007
• 发表时间: 2017-01
• 期刊: Brain, Behavior, and Immunity
• 作者: D. Peterlik;Christina Stangl;Amélie Bauer;A. Bludau;J. Keller;Dominik Grabski;Tobias Killian;D. Schmidt;Franziska Zajicek;G. Jaeschke;L. Lindemann;S. Reber;P. Flor;Nicole Uschold-Schmidt

Relief from detrimental consequences of chronic psychosocial stress in mice deficient for the metabotropic glutamate receptor subtype 7

缓解代谢型谷氨酸受体亚型 7 缺陷小鼠慢性社会心理压力的有害后果

• DOI: 10.1016/j.neuropharm.2016.04.036
• 期刊: Neuropharmacology
• 影响因子: 4.7
• 作者: Peterlik D;Stangl C;Bludau A;Grabski D;Strasser R;Schmidt D;Flor PJ;Uschold-Schmidt N
• 通讯作者: Uschold-Schmidt N

Metabotropic Glutamate Receptor Subtype 7 in the Bed Nucleus of the Stria Terminalis is Essential for Intermale Aggression

• DOI: 10.1038/npp.2015.198
• 发表时间: 2016-02-01
• 期刊: NEUROPSYCHOPHARMACOLOGY
• 影响因子: 7.6
• 作者: Masugi-Tokita, Miwako;Flor, Peter J.;Kawata, Mitsuhiro
• 通讯作者: Kawata, Mitsuhiro