Variant brain-derived neurotrophic factor (Valine66Methionine) polymorphism contributes to developmental and estrous stage-specific expression of anxiety-like behavior in female mice.
Variant brain-derived neurotrophic factor (Valine66Methionine) polymorphism contributes to developmental and estrous stage-specific expression of anxiety-like behavior in female mice.
复制标题
DOI：
10.1016/j.biopsych.2012.03.032
复制
发表时间：
2012-09-15
影响因子：
10.6
通讯作者：
Lee, Francis S.
中科院分区：
文献类型：
--
作者：
Bath, Kevin G.;Chuang, Jocelyn;Spencer-Segal, Joanna L.;Amso, Dima;Altemus, Margaret;McEwen, Bruce S.;Lee, Francis S.
大多数焦虑和抑郁症在女性中的发病率是男性的两倍，患病率的性别差异通常出现在青春期。整个月经周期以及产后和围绝经期的激素变化与焦虑和抑郁症状的风险增加有关。在人类和动物中，脑源性神经营养因子（BDNF）的减少与情感病理学的表达增加有关。最近，BDNF基因（BDNF Val66Met）中的单核苷酸多态性（SNP）降低了BDNF的生物利用度，已在人类中被鉴定并与多种神经精神疾病相关。虽然BDNF表达可以直接受到雌激素和孕激素的影响，但BDNF Val66Met SNP对生殖激素变化敏感性的潜在影响仍然是一个悬而未决的问题。作为预测模型，我们使用了将人SNP（BDNF Val66Met）插入小鼠BDNF基因的雌性小鼠。使用标准的行为模式，我们测试了这种SNP对焦虑样行为的年龄和动情周期特异性表达的影响。BDNF Val66 Met SNP纯合子小鼠开始在青春期前和成年早期发育中表现出增加的焦虑样行为，在发情周期中表现出焦虑样行为的显著波动，并且成年小鼠与野生型小鼠的不同之处在于在发情周期中表现出焦虑样行为的显著波动，特别是在发情期期间表现出更多的焦虑样行为。这些研究结果的潜在作用，这种SNP在促进人类情感障碍的发育和生殖发育依赖性变化的影响。
Most anxiety and depressive disorders are twice as common in women compared to men and the sex difference in prevalence typically emerges during adolescence. Hormonal changes across the menstrual cycle and during the postpartum and peri-menopausal periods are associated with increased risk for anxiety and depression symptoms. In humans and animals, reduced brain derived neurotrophic factor (BDNF) has been associated with increased expression of affective pathology. Recently, a single nucleotide polymorphism (SNP) in the BDNF gene (BDNF Val66Met), which reduces BDNF bioavailability, has been identified in humans and associated with a variety of neuropsychiatric disorders. Although BDNF expression can be directly influenced by estrogen and progesterone, the potential impact of the BDNF Val66Met SNP on sensitivity to reproductive hormone changes remains an open question. As a predictive model, we used female mice in which the human SNP (BDNF Val66Met) was inserted into the mouse BDNF gene. Using standard behavioral paradigms, we tested the impact of this SNP on age and estrous-cycle specific expression of anxiety-like behaviors. Mice homozygous for the BDNF Val66Met SNP begin to exhibit increased anxiety-like behaviors over prepubertal and early adult development, show significant fluctuations in anxiety-like behaviors over the estrous cycle, and as adults differ from wild-type mice by showing significant fluctuations in anxiety-like behaviors over the estrous cycle, specifically more anxiety-like behaviors during the estrus phase. These findings have implications regarding the potential role of this SNP in contributing to developmental and reproductive hormone-dependent changes in affective disorders in humans.
登录
查看更多内容
DOI：
10.1017/s1461145709000017
发表时间：
2009-08-01
影响因子：
4.8
作者：
Deltheil, Thierry;Tanaka, Kenji;Gardier, Alain M.
通讯作者：
Gardier, Alain M.
影响因子：
10.6
作者：
Joffe, H;Cohen, LS
通讯作者：
Cohen, LS
影响因子：
5.3
作者：
Chen, ZY;Ieraci, A;Lee, FS
通讯作者：
Lee, FS
影响因子：
10.6
作者：
Dwivedi, Yogesh;Rizavi, Hooriyah S.;Zhang, Hui;Mondal, Amal C.;Roberts, Rosalinda C.;Conley, Robert R.;Pandey, Ghanshyam N.
通讯作者：
Pandey, Ghanshyam N.
影响因子：
5.3
作者：
Hariri, AR;Goldberg, TE;Weinberger, DR
通讯作者：
Weinberger, DR