Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.
Serotonin deficiency alters susceptibility to the long-term consequences of adverse early life experience.
复制标题
DOI：
10.1016/j.psyneuen.2014.12.019
复制
发表时间：
2015-03
影响因子：
3.7
通讯作者：
Caron, Marc G.
中科院分区：
文献类型：
--
作者：
Sachs, Benjamin D.;Rodriguiz, Ramona M.;Tran, Ha L.;Iyer, Akshita;Wetsel, William C.;Caron, Marc G.
脑5-HT缺乏长期以来一直与精神疾病有关，但5-HT缺乏对应激易感性的影响在很大程度上仍然未知。早期生活压力（ELS）已被认为有助于成人精神病理学，但由于缺乏适当的临床前模型，研究ELS的长期后果的努力受到限制。在这里，我们评估了5-HT缺乏对小鼠对ELS新模型的几种长期细胞，分子和行为反应的影响，该模型结合了幼鼠的早期母体分离（MS）和产后习得性无助（LH）训练。我们的数据表明，这种模式（LH/MS）诱导抑郁样行为和损害小狗检索在大坝。此外，我们表明，大脑5-HT缺乏加剧焦虑样行为诱导的LH/MS和钝化的影响LH/MS对成年后代的声惊吓反应。虽然这些影响的机制尚不清楚，LH/MS后，5-HT缺乏的动物有显着减少盐皮质激素受体的mRNA表达在杏仁核比野生型动物。此外，5-HT缺陷小鼠表现出海马中5-HT 2a受体和p11的mRNA水平降低，而与应激无关。LH/MS减少了野生型（WT）和5-HT缺陷动物海马中doublecortin+未成熟神经元的数量。我们的数据强调了遗传因素和早期生活经验之间复杂的相互作用在调节情绪行为长期变化方面的重要性。这些发现可能对我们理解5-HT缺乏、ELS和产后抑郁症对神经精神疾病发展的组合作用具有重要意义。
Brain 5-HT deficiency has long been implicated in psychiatric disease, but the effects of 5-HT deficiency on stress susceptibility remain largely unknown. Early life stress (ELS) has been suggested to contribute to adult psychopathology, but efforts to study the long-term consequences of ELS have been limited by a lack of appropriate preclinical models. Here, we evaluated the effects of 5-HT deficiency on several long-term cellular, molecular, and behavioral responses of mice to a new model of ELS that combines early-life maternal separation (MS) of pups and postpartum learned helplessness (LH) training in dams. Our data demonstrate that this paradigm (LH/MS) induces depressive-like behavior and impairs pup retrieval in dams. In addition, we show that brain 5-HT deficiency exacerbates anxiety-like behavior induced by LH/MS and blunts the effects of LH/MS on acoustic startle responses in adult offspring. Although the mechanisms underlying these effects remain unclear, following LH/MS, 5-HT-deficient animals had significantly less mRNA expression of the mineralocorticoid receptor in the amygdala than wild-type animals. In addition, 5-HT-deficient mice exhibited reduced mRNA levels of the 5-HT2a receptor and p11 in the hippocampus regardless of stress. LH/MS decreased the number of doublecortin+ immature neurons in the hippocampus in both wild-type (WT) and 5-HT-deficient animals. Our data emphasize the importance of complex interactions between genetic factors and early life experience in mediating long-term changes in emotional behavior. These findings may have important implications for our understanding of the combinatorial roles of 5-HT deficiency, ELS, and postpartum depression on the development of neuropsychiatric disorders.
登录
查看更多内容
影响因子：
10.6
作者：
Bath, Kevin G.;Chuang, Jocelyn;Spencer-Segal, Joanna L.;Amso, Dima;Altemus, Margaret;McEwen, Bruce S.;Lee, Francis S.
通讯作者：
Lee, Francis S.
早期生活节目和神经发育障碍。
影响因子：
10.6
作者：
Bale, Tracy L.;Baram, Tallie Z.;Brown, Alan S.;Goldstein, Jill M.;Insel, Thomas R.;McCarthy, Margaret M.;Nemeroff, Charles B.;Reyes, Teresa M.;Simerly, Richard B.;Susser, Ezra S.;Nestler, Eric J.
通讯作者：
Nestler, Eric J.
影响因子：
4.8
作者：
Klok, Melanie D.;Alt, Simone R.;DeRijk, Roel H.
通讯作者：
DeRijk, Roel H.
DOI：
10.1097/00004583-200101000-00012
发表时间：
2001-01-01
影响因子：
13.3
作者：
Carter, AS;Garrity-Rokous, FE;Briggs-Gowan, MJ
通讯作者：
Briggs-Gowan, MJ
影响因子：
17.7
作者：
Bogdan, Ryan;Williamson, Douglas E.;Hariri, Ahmad R.
通讯作者：
Hariri, Ahmad R.