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

5-HT1a 过表达 mi 中的母亲行为和父系关系的影响

• 批准号: 7462642
• 负责人: Juan F Lopez
• 金额: $ 22.19万
• 依托单位: UNIVERSITY OF MICHIGAN AT ANN ARBOR
• 依托单位国家: 美国
• 财政年份: 2009
• 资助国家: 美国
• 起止时间: 2009-06-08 至 2011-05-31
• 项目状态: 已结题
• 来源: https://reporter.nih.gov/project-details/7462642
• 关键词: Adult; Affect; Affective; Animal Model; Animals; Anogenital region; Anti-Anxiety Agents; Anxiety; Anxiety Disorders; Applications Grants; Area; Bacterial Artificial Chromosomes; Behavior; Behavioral; Binding; Body Surface; Brain; Buffers; Caring; Characteristics; Child; Cognitive; Data; Defecation; Development; Discipline of Nursing; Down-Regulation; Emotional; Ensure; Environment; Esthesia; Exhibits; Female; Foundations; Future; Gender; Gene Expression; Genes; Genetic; Genital system; Goals; Grooming; Growth; Hand; Hippocampus (Brain); Hormonal; Hour; Human; Impairment; Investigation; Laboratories; Left; Link; Maternal Behavior; Measures; Mediating; Mental Health; Milk; Milk Ejection; Modeling; Mood Disorders; Moods; Mother-Child Relations; Mothers; Motor Activity; Mus; Mutation; Nature; Neurobiology; Neurons; Neuropeptides; Neurosecretory Systems; Neurotransmitters; Newborn Infant; Nipples; Odors; Oral cavity; Organism; Outcome; Oxytocin; Oxytocin Receptor; Pathogenesis; Phenotype; Physiological; Plant Roots; Play; Postpartum Period; Posture; Pregnancy; Process; Rattus; Research; Retrieval; Rodent; Role; Running; Serotonin; Serotonin Receptor 5-HT1A; Sex Behavior; Sex Characteristics; Shelter facility; Somatotropin; Specificity; Stimulus; Stress; System; Tactile; Testing; Time; Transgenic Animals; Transgenic Mice; Transgenic Organisms; Vision; affiliative behavior; behavior influence; behavior test; clinically significant; depressive symptoms; feeding; gene environment interaction; male; model development; mouse model; neonate; neural circuit; neurochemistry; novel; offspring; overexpression; pregnant; prevent; protective effect; public health relevance; pup; receptor; receptor binding; receptor expression; research study; response; salt balance; sensory stimulus; sex; social; social attachment; sound; tool

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.

描述（由申请人提供）：产妇护理中的障碍与后代情感和认知发展的障碍有关。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交、情感和认知发展有负面影响。遗传、激素和环境影响被认为在抑郁症和焦虑症的发展中起作用，特别是在产后时期。因此，了解可能诱发产后情绪障碍和影响产妇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，在海马中过度表达5-羟色胺1a （5-HT1a）受体。我们的初步数据表明：1)转基因雌性小鼠在产后表现出明显的母性行为障碍；2)这种母亲行为的损害与焦虑样行为的增加有关；3)类焦虑行为仅限于产后。未怀孕的处女没有表现出任何焦虑或抑郁的行为；4)在产前和产后期间，如果男性伴侣与女性在一起，可以预防产妇行为的损害。这个探索性/发展性R21应用程序旨在：1)进一步研究这些动物的产后行为表型（Specific Aim 1）； 2)开始描述一些可能与母亲行为受损相关的神经化学变化，以及该模型中伴侣的“保护”作用（Specific Aim 2）。研究结果将为未来研究5-HT1a过表达影响母亲行为的机制，以及社会联系如何缓冲这种基因改变的行为影响奠定基础。希望该动物模型将成为了解可能影响产后情绪和焦虑障碍发展的特定基因-环境相互作用的有用工具，并可能调节产妇护理的表达。因此，这个应用程序与PA-06-334的目标一致。公共卫生相关性：产妇护理的紊乱与后代情感和认知发育的损害有关。本应用程序旨在研究一种特定的5 -羟色胺分子，5 -羟色胺1a受体，对母体行为的作用，使用小鼠模型，在大脑中过度表达5 -羟色胺1a。希望该动物模型将成为理解调节母性关怀表达的特定基因-环境相互作用的有用工具。