Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment.
Stress-induced changes of hippocampal NMDA receptors: modulation by duloxetine treatment.
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DOI：
10.1371/journal.pone.0037916
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发表时间：
2012
期刊：
影响因子：
3.7
通讯作者：
Riva MA
中科院分区：
文献类型：
--
作者：
Calabrese F;Guidotti G;Molteni R;Racagni G;Mancini M;Riva MA
现在已经确定谷氨酸能系统参与抑郁症的病理生理。压力是抑郁症的一个主要诱发因素，压力会增加谷氨酸的释放，从而导致抑郁症患者大脑结构异常。另一方面，已经证明NMDA拮抗剂，如氯胺酮，在临床前和临床水平上发挥抗抑郁作用。在此基础上，我们的研究目的是调查慢性轻度应激是否与成年大鼠NMDA受体复合物的特异性改变有关，并确定伴随抗抑郁治疗是否可以使这种缺陷正常化。我们发现慢性应激在转录和翻译水平上增加了必需GluN1亚基以及辅助GluN2A和GluN2B亚基的表达，特别是在腹侧海马。与抗抑郁药度洛西汀同时治疗能够使谷氨酸受体亚基表达的增加正常化，并纠正应激暴露引起的受体磷酸化的变化。我们的数据表明，长期的应激（一种与抑郁症病因相关的状况）可能通过突触后机制，通过调节NMDA受体，增强谷氨酸活性，而抗抑郁药可能在一定程度上使这种变化正常化。我们的研究结果支持了抗抑郁药可能通过调节谷氨酸突触长期发挥其活性的观点。
It is now well established that the glutamatergic system contributes to the pathophysiology of depression. Exposure to stress, a major precipitating factor for depression, enhances glutamate release that can contribute to structural abnormalities observed in the brain of depressed subjects. On the other hand, it has been demonstrated that NMDA antagonists, like ketamine, exert an antidepressant effect at preclinical and clinical levels. On these bases, the purpose of our study was to investigate whether chronic mild stress is associated with specific alterations of the NMDA receptor complex, in adult rats, and to establish whether concomitant antidepressant treatment could normalize such deficits. We found that chronic stress increases the expression of the obligatory GluN1 subunit, as well as of the accessory subunits GluN2A and GluN2B at transcriptional and translational levels, particularly in the ventral hippocampus. Concomitant treatment with the antidepressant duloxetine was able to normalize the increase of glutamatergic receptor subunit expression, and correct the changes in receptor phosphorylation produced by stress exposure. Our data suggest that prolonged stress, a condition that has etiologic relevance for depression, may enhance glutamate activity through post-synaptic mechanisms, by regulating NMDA receptors, and that antidepressants may in part normalize such changes. Our results provide support to the notion that antidepressants may exert their activity in the long-term also via modulation of the glutamatergic synapse.
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影响因子：
64.8
作者：
Autry, Anita E.;Adachi, Megunai;Nosyreva, Elena;Na, Elisa S.;Los, Maarten F.;Cheng, Peng-fei;Kavalali, Ege T.;Monteggia, Lisa M.
通讯作者：
Monteggia, Lisa M.
影响因子：
16.2
作者：
Fanselow, Michael S.;Dong, Hong-Wei
通讯作者：
Dong, Hong-Wei
DOI：
10.1126/science.1190287
发表时间：
2010-08-20
期刊：
Science (New York, N.Y.)
影响因子：
--
作者：
Li N;Lee B;Liu RJ;Banasr M;Dwyer JM;Iwata M;Li XY;Aghajanian G;Duman RS
通讯作者：
Duman RS
影响因子：
4.7
作者：
MOGHADDAM, B
通讯作者：
MOGHADDAM, B
影响因子：
34.7
作者：
Krugers, Harmen J.;Hoogenraad, Casper C.;Groc, Laurent
通讯作者：
Groc, Laurent