Neural Basis of Stress-Derailed Motherhood

压力脱轨母性的神经基础

• 批准号: 10666891
• 负责人: Joseph S Lonstein
• 金额: $ 20.12万
• 依托单位: MICHIGAN STATE UNIVERSITY
• 依托单位国家: 美国
• 财政年份: 2023
• 资助国家: 美国
• 起止时间: 2023-04-01 至 2025-03-31
• 项目状态: 未结题
• 来源: https://reporter.nih.gov/project-details/10666891
• 关键词: Affect; Affective; Anxiety; Autoradiography; Basic Science; Behavior; Birth; Brain; CRF receptor type 1; Caring; Cells; Chemicals; Corticotropin-Releasing Hormone; Corticotropin-Releasing Hormone Receptors; Data; Development; Dorsal; Down-Regulation; Electrophysiology (science); Ensure; Female; Future; Genes; Goals; Hormonal; Immunohistochemistry; Impairment; In Situ Hybridization; Infant; Infant Care; Intervention; Knowledge; Label; Laboratories; Laboratory Rat; Lactation; Life Stress; Ligands; Measures; Mediating; Mental Health; Mental disorders; Messenger RNA; MicroRNAs; Midbrain structure; Modeling; Mothers; Neurobiology; Neurons; Neuropeptides; Neurotransmitters; Perinatal; Phenotype; Postpartum Period; Postpartum Women; Pregnancy; Pregnant Women; Process; Prosencephalon; Quantitative Reverse Transcriptase PCR; Rattus; Reproduction; Research; Research Methodology; Rodent; Serotonergic System; Serotonin; Sex Differences; Signal Transduction; Signaling Molecule; Site; Slice; Source; Stress; System; Technology; Testing; Time; Viral Vector; Woman; abuse neglect; anxiety symptoms; anxiety-like behavior; behavioral impairment; caregiving; depressive symptoms; dorsal raphe nucleus; gamma-Aminobutyric Acid; high risk; improved; innovation; male; maternal anxiety; maternal caregiving; maternal depression; maternal stress; motherhood; negative affect; neural; neurochemistry; neuromechanism; post pregnancy; pregnant; prevent; protein expression; receptor; receptor expression; response; tool; transmission process; virtual

PROJECT SUMMARY Becoming a mother is often associated with a unique sense of joy, serenity, and personal fulfillment. A tremendous number of pregnant and postpartum women cannot reach these positive states, though, because they struggle with high levels of life stress. High pregnancy stress degrades women’s later ability to sensitively care for their infants, and in very severe cases contributes to infant neglect and abuse. In addition, elevated stress during pregnancy is one of the most reliable and strongest predictors of maternal depression and anxiety, which afflict 10-15% of the four million pregnant and recently parturient women in the U.S. each year. There is a dearth of knowledge about the specific neural mechanisms through which stress contributes to maternal depression, anxiety, and poor infant caregiving. Without such knowledge, it is virtually impossible to know how to best intervene or treat women who are at the highest risk. The long-term goal of this line of basic research is to better understand how stress during pregnancy derails postpartum behavior by affecting interactions between the stress-signaling neuropeptide, corticotropin releasing factor (CRF), and the neurotransmitter, serotonin (5-HT). The objective of this R21 exploratory/developmental project is to use a laboratory rat model of motherhood to begin testing the hypothesis that female reproduction generates normative changes in CRF receptors in the midbrain dorsal raphe nucleus (i.e., the source of most forebrain 5- HT), and that these changes are derailed by pregnancy stress. I further hypothesize that the normative changes across reproduction in CRF receptors in the DR protect mothers against the negative consequences of stress on their affective and caregiving behaviors. The proposed multi-method research employs a variety of tools to answer our questions (qRT-PCR, receptor autoradiography, dual-label in situ hybridization, slice electrophysiology, viral vector-mediated gene up/downregulation, detailed behavior analysis) and is innovative because it the first to study how stressed and unstressed female reproduction affect CRF receptors site- specifically in the serotonergic dorsal raphe, and more broadly to provide critical information about the neurochemistry underlying stress’ impact on the female brain and behavior. This important basic research is highly significant because our results have the potential to improve strategies for intervention and treatment of the millions of women and their infants negatively affected by pregnancy stress each year.

项目摘要 成为母亲通常与独特的欢乐，宁静和个人成就感有关。一个 但是，大量孕妇和产后妇女无法达到这些积极的状态 他们在高水平的生活压力下挣扎。高怀孕压力会使女性随后敏感的能力降低 照顾婴儿，并且在非常严重的情况下会导致婴儿忽视和虐待。另外，升高 怀孕期间的压力是孕产妇抑郁症的最可靠，最有力的预测因素之一 焦虑症，每年在美国的四百万怀孕和最近对妇女的焦虑中折磨10-15％。 关于特定神经机制的知识死亡，压力导致压力有助于 孕产妇抑郁，焦虑和婴儿护理不良。没有这样的知识，几乎不可能 知道如何最好地干预或治疗风险最高的妇女。这条基本线的长期目标 研究是为了更好地了解怀孕期间的压力如何通过影响产后行为 应激信号神经肽，皮质激素释放因子（CRF）与 神经递质，5-羟色胺（5-HT）。该R21探索性/发展项目的目的是使用 孕育的实验室大鼠模型开始检验女性繁殖产生的假设 中脑背raphe核中CRF受体的正常变化（即，大多数前脑5--的来源 HT），并且这些变化因妊娠压力而脱轨。我进一步假设正常 DR保护母亲免受负面后果的CRF受体繁殖的变化 压力他们的情感和照料行为。拟议的多方法研究员工各种各样 回答我们的问题的工具（QRT-PCR，受体放射自显影，双标签原位杂交，切片 电生理学，病毒载体介导的基因向上/下调，详细的行为分析），是创新的 因为这是第一个研究压力和无压力女性繁殖如何影响CRF受体部位的方式 - 特别是在血清素能背带，更广泛地提供有关有关的关键信息 神经化学对女性大脑和行为的影响。这项重要的基础研究是 非常重要的是，因为我们的结果有可能改善干预和治疗的策略 每年，数以百万计的妇女及其婴儿对怀孕压力产生负面影响。