Social stress induces neurovascular pathology promoting depression.
Social stress induces neurovascular pathology promoting depression.
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DOI：
10.1038/s41593-017-0010-3
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发表时间：
2017-12
影响因子：
25
通讯作者：
Russo SJ
中科院分区：
文献类型：
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作者：
Menard C;Pfau ML;Hodes GE;Kana V;Wang VX;Bouchard S;Takahashi A;Flanigan ME;Aleyasin H;LeClair KB;Janssen WG;Labonté B;Parise EM;Lorsch ZS;Golden SA;Heshmati M;Tamminga C;Turecki G;Campbell M;Fayad ZA;Tang CY;Merad M;Russo SJ
研究表明，外周炎症加剧有助于抑郁症的发病机制。我们研究了慢性社会失败应激（一种抑郁症小鼠模型）对血脑屏障（BBB）通透性和外周免疫信号浸润的影响。我们发现应激易感小鼠伏隔核（NAc）内皮细胞紧密连接蛋白cldn5 （cldn5）表达减少，血管形态异常。抑郁症患者NAc中CLDN5的表达也有所下降。Cldn5下调足以诱导阈下社会压力后的抑郁样行为，而慢性抗抑郁治疗可挽救Cldn5缺失并促进恢复力。应激易感或注射aav - shrna -cldn5小鼠NAc血脑屏障完整性降低，导致外周细胞因子白介素-6 （IL-6）向脑实质浸润，随后表达抑郁样行为。这些发现表明，慢性社会压力通过失去紧密连接蛋白cldn5改变血脑屏障的完整性，促进外周IL-6通过血脑屏障和抑郁。
Studies suggest that heightened peripheral inflammation contributes to the pathogenesis of major depressive disorder. We investigated the effect of chronic social defeat stress, a mouse model of depression, on blood-brain barrier (BBB) permeability and infiltration of peripheral immune signals. We found reduced expression of endothelial cell tight junction protein claudin-5 (cldn5) and abnormal blood vessel morphology in nucleus accumbens (NAc) of stress-susceptible but not resilient mice. CLDN5 expression was also decreased in NAc of depressed patients. Cldn5 down-regulation was sufficient to induce depression-like behaviors following subthreshold social stress while chronic antidepressant treatment rescued cldn5 loss and promoted resilience. Reduced BBB integrity in NAc of stress-susceptible or AAV-shRNA-cldn5-injected mice caused infiltration of peripheral cytokine interleukin-6 (IL-6) into brain parenchyma and subsequent expression of depression-like behaviors. These findings suggest that chronic social stress alters BBB integrity through loss of tight junction protein cldn5, promoting peripheral IL-6 passage across the BBB and depression.
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影响因子：
82.9
作者：
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影响因子：
10.6
作者：
Dowlati, Yekta;Herrmann, Nathan;Lanctot, Krista L.
通讯作者：
Lanctot, Krista L.
影响因子：
64.8
作者：
Golden SA;Heshmati M;Flanigan M;Christoffel DJ;Guise K;Pfau ML;Aleyasin H;Menard C;Zhang H;Hodes GE;Bregman D;Khibnik L;Tai J;Rebusi N;Krawitz B;Chaudhury D;Walsh JJ;Han MH;Shapiro ML;Russo SJ
通讯作者：
Russo SJ
影响因子：
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作者：
Kessler, RC;Berglund, P;Walters, EE
通讯作者：
Walters, EE
DOI：
10.1038/npp.2016.169
发表时间：
2017-01
期刊：
Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology
影响因子：
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作者：
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