Relief from detrimental consequences of chronic psychosocial stress in mice deficient for the metabotropic glutamate receptor subtype 7
Relief from detrimental consequences of chronic psychosocial stress in mice deficient for the metabotropic glutamate receptor subtype 7
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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
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发表时间：
--
影响因子：
4.7
通讯作者：
Uschold-Schmidt N
中科院分区：
文献类型：
--
作者：
Peterlik D;Stangl C;Bludau A;Grabski D;Strasser R;Schmidt D;Flor PJ;Uschold-Schmidt N
慢性应激相关的精神疾病和共病的躯体病理在现代社会是一个巨大的公共卫生问题。这些疾病的病因是复杂的，应激源具有慢性和心理社会成分，是最公认的危险因素。在过去的几十年里，对代谢型谷氨酸受体(MGlu)系统的研究取得了很大进展，代谢型谷氨酸受体7亚型(MGlu7)在急性应激相关行为和生理中的作用受到了越来越多的关注。然而，关于mGlu7在慢性心理社会压力相关疾病中的潜在作用，我们几乎一无所知。利用雄性小鼠的慢性从属群体住房(CSC，19天)，我们研究了中心mGlu7是否在慢性心理社会应激源暴露时发生改变，以及mGlu7的遗传消融是否干扰了大量的慢性应激诱导的改变。CSC暴露导致前额叶皮质mGlu7mRNA转录水平下调，这是一个与应激相关行为和生理相关的大脑区域。有趣的是，mGlu7缺乏缓解了多种慢性应激诱导的改变，包括CSC诱导的易焦虑表型；mGlu7消融还分别改善了CSC诱导的生理和免疫后果，如下丘脑-垂体-肾上腺(HPA)轴功能障碍和结肠炎。总之，我们的发现提供了第一个证据，证明mGlu7参与了响应慢性心理社会应激源暴露的广泛的行为和生理变化。此外，mGlu7基因消融的应激保护表型表明，mGlu7药物阻断是治疗慢性应激相关情绪和躯体功能障碍的相关选择。本文是题为《代谢性谷氨酸受体，5年来》的特刊的一部分。
Chronic stress-related psychiatric conditions and comorbid somatic pathologies are an enormous public health concern in modern society. The etiology of these disorders is complex, with stressors holding a chronic and psychosocial component representing the most acknowledged risk factor. During the last decades, research on the metabotropic glutamate receptor (mGlu) system advanced dramatically and much attention was given to the role of the metabotropic glutamate receptor subtype 7 (mGlu7) in acute stress-related behavior and physiology. However, virtually nothing is known about the potential involvement of mGlu7 in chronic psychosocial stress-related conditions. Using the chronic subordinate colony housing (CSC, 19 days) in male mice, we addressed whether central mGlu7 is altered upon chronic psychosocial stressor exposure and whether genetic ablation of mGlu7 interferes with the multitude of chronic stress-induced alterations. CSC exposure resulted in a downregulation of mGlu7 mRNA transcript levels in the prefrontal cortex, a brain region relevant for stress-related behaviors and physiology. Interestingly, mGlu7 deficiency relieved multiple chronic stress-induced alterations including the CSC-induced anxiety-prone phenotype; mGlu7 ablation also ameliorated CSC-induced physiological and immunological consequences such as hypothalamo-pituitary-adrenal (HPA) axis dysfunctions and colonic inflammation, respectively. Together, our findings provide first evidence for the involvement of mGlu7 in a wide range of behavioral and physiological alterations in response to chronic psychosocial stressor exposure. Moreover, the stress-protective phenotype of genetic mGlu7 ablation suggests mGlu7 pharmacological blockade to be a relevant option for the treatment of chronic stress-related emotional and somatic dysfunctions.This article is part of the Special Issue entitled ‘Metabotropic Glutamate Receptors, 5 years on’.
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代谢型谷氨酸受体亚型 7 消融导致恐惧反应和条件性味觉厌恶缺陷
影响因子：
5.3
作者：
M. Masugi;M. Yokoi;R. Shigemoto;K. Muguruma;Yasuyoshi Watanabe;G. Sansig;H. van der Putten;S. Nakanishi
通讯作者：
S. Nakanishi
影响因子：
24
作者：
Dimsdale, Joel E.
通讯作者：
Dimsdale, Joel E.
附属群体（CSC）住房引起的慢性社会心理应激对小鼠脑神经元活动模式的影响
影响因子：
2.3
作者：
G. Singewald;N. K. Nguyen;I. Neumann;N. Singewald;S. Reber
通讯作者：
S. Reber
海马 mGluR5 预测重复暴露于无法控制的压力后会出现无助行为
影响因子：
2.5
作者：
Y. S. Yim;Jinu Lee;G. Kim;T. Song;C. Kim;Dong Goo Kim
通讯作者：
Dong Goo Kim
影响因子：
2.3
作者：
DUFFY, LC;ZIELEZNY, MA;GRAHAM, S
通讯作者：
GRAHAM, S