Environmental perturbation of the circadian clock during pregnancy leads to transgenerational mood disorder-like behaviors in mice.
Environmental perturbation of the circadian clock during pregnancy leads to transgenerational mood disorder-like behaviors in mice.
复制标题
怀孕期间生物钟的环境扰动导致小鼠出现跨代情绪障碍样行为
DOI：
10.1038/s41598-017-13067-y
复制
发表时间：
2017-10-03
影响因子：
4.6
通讯作者：
Cheng HM
中科院分区：
文献类型：
--
作者：
Zhang P;Li G;Li H;Tan X;Cheng HM
目前尚不清楚怀孕期间的慢性昼夜节律紊乱（CCD）是否会导致后代的情绪障碍。本研究表明，暴露于CCD应激的F0代怀孕小鼠表现出类似抑郁的行为，而F1和F2代的后代也表现出与情绪相关的行为表型，尽管它们在出生后或成年期缺乏直接的应激经历。产前CCD应激与F1小鼠血浆皮质酮水平升高相关。此外，F1小鼠视交叉上核核心生物钟基因的昼夜表达谱被破坏。蛋白质组学分析显示，产前CCD应激导致雌性F1小鼠下丘脑蛋白表达发生明显变化，特别是与细胞活动、代谢、发育和疾病相关的蛋白。在CCD F1代中，黑素皮质素4受体的表达存在明显的性别差异。我们得出的结论是，母亲在怀孕期间暴露于慢性昼夜节律紊乱可导致性别特异性情绪障碍，并持续至少两代子女。潜在的机制可能取决于血浆皮质酮水平、昼夜节律和下丘脑蛋白表达的代际变化。
It remains unknown whether chronic circadian disturbance (CCD) during pregnancy can lead to mood disorders in the offspring. Here we show that pregnant mice in the F0 generation that were exposed to CCD stress displayed depression-like behaviors, and produced offspring in the F1 and F2 generations that also exhibited mood-associated behavioral phenotypes despite the lack of direct stressful experiences during their postnatal or adult period. Prenatal CCD stress was correlated with the elevation of plasma corticosterone levels in F1 mice. Furthermore, the diurnal expression profiles of core circadian clock genes were disrupted in the suprachiasmatic nucleus of F1 mice. Proteomics analysis revealed that prenatal CCD stress resulted in distinct changes in protein expression in the hypothalamus of female F1 mice, in particular proteins that were associated with cellular activities, metabolism, development and diseases. Sex-specific differences in melanocortin 4 receptor expression were apparent in the CCD F1 generation. We conclude that maternal exposure to chronic circadian disturbance during pregnancy can lead to sex-specific mood disorders that persist for at least two filial generations. The underlying mechanisms may depend on transgenerational changes in plasma corticosterone levels, circadian pacemaking, and hypothalamic protein expression.
登录
查看更多内容
影响因子：
10.6
作者：
Dong E;Dzitoyeva SG;Matrisciano F;Tueting P;Grayson DR;Guidotti A
通讯作者：
Guidotti A
影响因子：
3.7
作者：
Flo E;Pallesen S;Magerøy N;Moen BE;Grønli J;Hilde Nordhus I;Bjorvatn B
通讯作者：
Bjorvatn B
影响因子：
3.7
作者：
Koizumi H;Kurabayashi N;Watanabe Y;Sanada K
通讯作者：
Sanada K
影响因子：
5.6
作者：
Liu C;Chung M
通讯作者：
Chung M
影响因子：
6.1
作者：
BIEGON, A;RECHES, A;MCEWEN, BS
通讯作者：
MCEWEN, BS