Maternal behavior and effects of paternal affiliation in 5-HT1a overexpressing mi

描述（由申请人提供）：母体护理障碍与后代情感和认知发育障碍相关。对于人类来说，越来越多的证据表明产后情绪障碍对母婴关系以及孩子的社交、情感和认知发展产生负面影响。遗传、激素和环境影响被认为在抑郁和焦虑症的发展中起作用，特别是在产后时期。因此，了解可能易患产后情绪障碍和影响母亲行为的神经生物学因素以及可能具有保护作用的因素具有很高的临床意义。我们最近开发了一种转基因小鼠模型，过度表达5-羟色胺1a（5-HT 1a）受体在海马。我们的初步数据表明，转基因雌性小鼠：1）在产后期间表现出明显的母性行为障碍; 2）这种母性行为障碍与焦虑样行为的增加有关; 3）焦虑样行为仅限于产后期间。未怀孕的处女女性不会表现出任何焦虑或抑郁的行为; 4）如果男性伴侣在产前和产后期间与女性保持在一起，则可以防止母性行为的损害。该探索性/开发性R21应用旨在：1）进一步研究这些动物的产后行为表型（具体目标1），2）开始表征可能与母体行为受损相关的一些神经化学变化，以及该模型中伴侣的“保护”作用（具体目标2）。这些结果将为未来研究5-HT 1a过度表达影响母亲行为的机制以及社会联系如何缓冲这种遗传改变的行为影响奠定基础。希望这种动物模型将是一个有用的工具，在了解特定的基因-环境相互作用，可能会影响产后情绪和焦虑症的发展，并可能调节产妇护理的表达。因此，本申请符合PA-06-334的目标。公共卫生相关性：母亲护理方面的障碍与后代情感和认知发展方面的障碍有关。本申请旨在研究特定的5-羟色胺分子，5-羟色胺1a受体，对母性行为的作用，使用在大脑中过度表达5-羟色胺1a的小鼠模型。希望这种动物模型将是一个有用的工具，在了解特定的基因-环境相互作用，调节母性关怀的表达。

DESCRIPTION (provided by applicant): Disturbances in maternal care have been associated with impairments in affective and cognitive development of the offspring. In humans, there is growing evidence that postpartum mood disorders have a negative impact on the mother-child relationship, and the child's social, emotional, and cognitive development. Genetic, hormonal, and environmental influences are believed to play a role in the development of depressive and anxiety disorders, particularly in the post-partum period. Understanding the neurobiological factor(s) that may predispose to postpartum mood disorders and affect maternal behavior, as well as the factors that may be protective are therefore, of high clinical significance. We have recently developed a transgenic mouse model that over-expresses the serotonin 1a (5-HT1a) receptor in hippocampus. Our preliminary data show that transgenic female mice: 1) exhibit significant impairments in maternal behavior in the post-partum period; 2) this impairment in maternal behavior is associated with increases in anxiety-like behavior; 3) the anxiety-like behavior is limited to the post-partum period. Non-pregnant virgin females do not exhibit any anxiety-like or depressive-like behaviors; 4) the impairments in maternal behavior are prevented if the male partner is kept with the female during the pre-partum and post-partum period. This exploratory/developmental R21 application seeks to: 1) further investigate the post-partum behavioral phenotype of these animals (Specific Aim 1), 2) begin to characterize some of the neurochemical changes that may be associated with impaired maternal behavior, and with the "protective" effect of the partner in this model (Specific Aim 2). The results will serve as a foundation for future studies investigating the mechanisms whereby 5-HT1a overexpression influences maternal behavior, and how social bonding buffers the behavioral impact of this genetic alteration. It is hoped that this animal model will be a useful tool in understanding the specific gene-environment interactions that may influence the development of post-partum mood and anxiety disorders, and may modulate the expression of maternal care. As such, this application is consistent with the goals of PA-06-334. PUBLIC HEALTH RELEVANCE: Disturbances in maternal care have been associated with impairments in the affective and cognitive development of the offspring. This application seeks to investigate the role of a specific serotonin molecule, the serotonin 1a receptor, on maternal behavior, using a mouse model that over-expresses serotonin 1a in brain. It is hoped that this animal model will be a useful tool in understanding the specific gene-environment interactions that modulate the expression of maternal care.