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

描述(由申请人提供)：母亲护理方面的障碍与子女的情感和认知发展障碍有关。在人类中，越来越多的证据表明，产后情绪障碍对母子关系以及孩子的社会、情感和认知发展都有负面影响。遗传、激素和环境的影响被认为在抑郁症和焦虑症的发展中发挥了作用，特别是在产后时期。因此，了解可能诱发产后情绪障碍并影响母亲行为的神经生物学因素(S)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，它在海马区过度表达5-HT1a(5-HT1A)受体。我们的初步数据显示：1)转基因雌性小鼠在产后表现出显著的母性行为障碍；2)这种母性行为的损害与焦虑样行为的增加有关；3)焦虑样行为仅限于产后时期。未怀孕的处女不会表现出任何类似焦虑或抑郁的行为；4)如果在产前和产后期间男方与女方在一起，母体行为的损害就会得到预防。这一探索性/发育性R21应用试图：1)进一步研究这些动物的产后行为表型(特定目标1)，2)开始表征一些神经化学变化，这些变化可能与母亲的行为受损有关，以及与该模型中伴侣的“保护”作用(特定目标2)有关。这一结果将成为未来研究5-HT1A过度表达影响母亲行为的机制，以及社会纽带如何缓冲这种基因变化对行为影响的基础。这一动物模型有望成为了解特定基因-环境相互作用的有用工具，这些基因-环境相互作用可能影响产后情绪和焦虑症的发展，并可能调节母体关怀的表达。因此，本申请符合PA-06-334的目标。公共卫生相关性：产妇护理方面的障碍与子代的情感和认知发育受损有关。这项应用试图利用在大脑中过度表达5-羟色胺1a的小鼠模型，研究特定的5-羟色胺分子--5-羟色胺1a受体在母性行为中的作用。人们希望这个动物模型将成为了解特定基因-环境相互作用的有用工具，这些基因-环境相互作用调节了母体关怀的表达。

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.