The roles of sex and serotonin transporter levels in age- and stress-related emotionality in mice.
The roles of sex and serotonin transporter levels in age- and stress-related emotionality in mice.
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DOI：
10.1016/j.brainres.2009.06.079
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发表时间：
2009-08-25
期刊：
影响因子：
2.9
通讯作者：
Sibille E
中科院分区：
文献类型：
--
作者：
Joeyen-Waldorf J;Edgar N;Sibille E
情绪障碍受基因构成的影响，对男性和女性的影响不同。血清素转运蛋白 (SERT) 基因中的 s/l 启动子多态性可调节人类的特质情绪和发展为抑郁状态的脆弱性。同样，缺乏 SERT（敲除/KO）的雄性小鼠表现出较高的情绪表型。我们现在报告说，SERT-KO 表型在整个成年后期都保持不变，并且雌性 KO 小鼠随着年龄的增长会产生更大的情绪表型。因此，为了检验这些发现反映了 SERT 介导的情绪调节中假定的性别二态性的假设，我们将成年雄性和雌性野生型、杂合子 (HZ) 和 KO 小鼠置于不可预测的慢性轻度应激 (UCMS) 下，并评估行为变化。在男性中，UCMS 后 SERT-KO 情绪相关行为的升高与其他群体趋同。相反，女性 SERT-KO 显示出正常的无压力基线，但 UCMS 诱发的情绪最高。 SERT-HZ 在两个实验中都显示出可变和中间表型。因此，不同生物模式（年龄、压力）的一致结果表明，SERT 基因型对男性基线“特质”情绪的贡献较高，而对女性的贡献较低。相比之下，年龄相关和压力引起的行为变化导致女性中 SERT 基因型介导的行为差异较高，但男性中较低。这表明，与女性相比，男性（高基线/特质）与低 SERT 相关的高情绪状态（更容易发展为高情绪）有差异。这种性别与 SERT 的双重解离提供了一个框架来研究与血清素功能相一致的情绪调节的分子底物，并可能导致情绪障碍的性别二态性特征。
Mood disorders are influenced by genetic make-up and differentially affect men and women. The s/ l promoter polymorphism in the serotonin transporter (SERT) gene moderates both trait emotion and the vulnerability to develop depressive states in humans. Similarly, male mice lacking SERT (Knockout/KO) display an elevated emotionality phenotype. We now report that the SERT-KO phenotype is maintained throughout late-adulthood, and that female KO mice develop a larger emotionality phenotype with increasing age. Thus, to test the hypothesis that these findings reflected a putative sexual dimorphism in SERT-mediated modulation of emotionality, we submitted adult male and female wild-type, heterozygous (HZ) and KO mice to unpredictable chronic mild stress (UCMS) and assessed behavioral changes. In males, the elevated SERT-KO emotion-related behavior converged with other groups after UCMS. Conversely, female SERT-KO displayed a normal non-stressed baseline, but highest UCMS-induced emotionality. SERT-HZ displayed variable and intermediate phenotypes in both experiments. Thus, consistent results across different biological modalities (age, stress) revealed a high contribution of SERT genotype for baseline “trait” emotionality in males, and low contribution for female. In contrast, age-correlated and stress-induced behavioral changes resulted in a high SERT genotype-mediated behavioral variance in females, but low in males. This suggests that high emotionality states associated with low SERT were differentially achieved in males (high baseline/trait) compared to females (increased vulnerability to develop high emotionality). This sex-by-SERT double dissociation provides a framework to investigate molecular substrates of emotionality regulation in concert with serotonin function and may contribute to the sexually dimorphic features of mood disorders.
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影响因子：
56.9
作者：
Santarelli, L;Saxe, M;Hen, R
通讯作者：
Hen, R
影响因子：
10.6
作者：
Holmes, A;Murphy, DL;Crawley, JN
通讯作者：
Crawley, JN
影响因子：
7
作者：
Lerer, B;Gillon, D;Shapira, B
通讯作者：
Shapira, B
DOI：
10.1073/pnas.0403763101
发表时间：
2004-08-17
影响因子：
11.1
作者：
Barr, CS;Newman, TK;Higley, JD
通讯作者：
Higley, JD
影响因子：
3.6
作者：
Bengel, D;Murphy, DL;Lesch, KP
通讯作者：
Lesch, KP