Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue.
Vascular and blood-brain barrier-related changes underlie stress responses and resilience in female mice and depression in human tissue.
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DOI：
10.1038/s41467-021-27604-x
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发表时间：
2022-01-10
影响因子：
16.6
通讯作者：
Menard C
中科院分区：
文献类型：
--
作者：
Dion-Albert L;Cadoret A;Doney E;Kaufmann FN;Dudek KA;Daigle B;Parise LF;Cathomas F;Samba N;Hudson N;Lebel M;Signature Consortium;Campbell M;Turecki G;Mechawar N;Menard C
抑郁症的患病率、症状和治疗表明，严重抑郁障碍(MDD)存在性别差异。社会应激诱导的神经血管病理与雄性小鼠的抑郁症状有关；然而，这种联系在雌性小鼠中尚不清楚。在这里，我们报告了慢性社会和亚慢性可变应激促进雌性小鼠情绪相关脑区血脑屏障(BBB)的改变。有针对性地破坏女性前额叶皮质(PFC)的血脑屏障会导致焦虑和抑郁的行为。通过比较雄性和雌性小鼠PFC的内皮细胞特异性转录图谱，我们确定了几条与不良适应应激反应和应激恢复有关的途径和基因。此外，我们还证实了应激雌性小鼠前额叶的血脑屏障是漏泄的。然后，我们确定了慢性应激的循环血管生物标志物，如可溶性E-选择素。在诊断为MDD的女性的血清和死后脑样本中，也可以发现循环中可溶性E-选择素、BBB基因表达和形态的类似变化。总之，我们认为BBB功能障碍在调节雌性小鼠和可能的MDD的应激反应中起着重要作用。情绪障碍的性别差异背后的血管、细胞和分子变化尚不清楚。在这里，作者表明，血脑屏障功能障碍调节雌性小鼠的焦虑和抑郁样行为，以及与适应不良反应相关的内皮特异性变化，而不是对压力的弹性。
Prevalence, symptoms, and treatment of depression suggest that major depressive disorders (MDD) present sex differences. Social stress-induced neurovascular pathology is associated with depressive symptoms in male mice; however, this association is unclear in females. Here, we report that chronic social and subchronic variable stress promotes blood-brain barrier (BBB) alterations in mood-related brain regions of female mice. Targeted disruption of the BBB in the female prefrontal cortex (PFC) induces anxiety- and depression-like behaviours. By comparing the endothelium cell-specific transcriptomic profiling of the mouse male and female PFC, we identify several pathways and genes involved in maladaptive stress responses and resilience to stress. Furthermore, we confirm that the BBB in the PFC of stressed female mice is leaky. Then, we identify circulating vascular biomarkers of chronic stress, such as soluble E-selectin. Similar changes in circulating soluble E-selectin, BBB gene expression and morphology can be found in blood serum and postmortem brain samples from women diagnosed with MDD. Altogether, we propose that BBB dysfunction plays an important role in modulating stress responses in female mice and possibly MDD. The vascular, cellular and molecular changes underlying sex differences in mood disorders are unclear. Here, the authors show that blood-brain barrier dysfunction modulates anxiety- and depressive-like behaviors in female mice and endothelium-specific changes associated with maladaptive responses compared to resilience to stress.
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影响因子：
20.1
作者：
Garcia M;Mulvagh SL;Merz CN;Buring JE;Manson JE
通讯作者：
Manson JE
影响因子：
7.6
作者：
Harris, Alexander Z.;Atsak, Piray;Gordon, Joshua A.
通讯作者：
Gordon, Joshua A.
影响因子：
3.3
作者：
Johnson, Alyssa;Rainville, Jennifer R.;Hodes, Georgia E.
通讯作者：
Hodes, Georgia E.
影响因子：
--
作者：
Kessler, RC;Berglund, P;Walters, EE
通讯作者：
Walters, EE
影响因子：
--
作者：
Barry, Lisa C.;Allore, Heather G.;Gill, Thomas M.
通讯作者：
Gill, Thomas M.