Effects of chronic stress in pregnancy on hypothalamic gene expression patterns: interference with antidepressants and identified pathways

妊娠期慢性应激对下丘脑基因表达模式的影响：抗抑郁药的干扰和已确定的途径

• 批准号: 50582534
• 负责人: Professorin Dr. Inga D. Neumann
• 金额: --
• 依托单位: Lehrstuhl für Neurobiologie und Tierphysiologie
• 依托单位国家: 德国
• 项目类别: Research Grants
• 财政年份: 2007
• 资助国家: 德国
• 起止时间: 2006-12-31 至 2015-12-31
• 项目状态: 已结题
• 来源: https://gepris.dfg.de/gepris/projekt/50582534?language=en
• 关键词: Effects; chronic; stress; pregnancy; hypothalamic

Complex peripartum adaptations at neuroendocrine, neuronal and behavioural levels are well-established, which are necessary to prepare the mother for birth and motherhood. This includes attenuated glucocorticoid responsiveness, despite a concurrent basal hypercorticism, increased activity of the oxytocinergic system, onset of maternal behaviour, and anxiolysis. These changes are essential for both the healthy development of the offspring as well as for the maternal mental health. Disturbances of these adaptations, for example by chronic stress, are likely to increase the vulnerability of postpartum mood disorders, but underlying mechanisms are unknown. Data from the initial funding period demonstrate that chronic pregnancy stress (PS) in rat dams prevents these pregnancy- and lactation-associated adaptations.In continuation of these and recent results we first aim to fully characterize reproductionrelated alterations in gene expression patterns within the hypothalamic paraventricular nucleus (a region highly involved in maternal and stress adaptations), and how these gene expression patterns are altered by PS. In turn, pharmacological manipulation, or restoration by chronic antidepressant treatment, of neuronal target pathways/systems identified to be altered by PS would reveal their causal role in PS-induced maladaptations. The results will importantly increase our understanding of adaptive and maladaptive peripartum alterations for the first time at the genetic and cellular levels.

围产期在神经内分泌、神经元和行为层面的复杂适应已经确立，这是母亲为分娩和为人母做好准备所必需的。这包括减弱的糖皮质激素反应性，尽管同时存在基础皮质功能亢进、催产素能系统活性增加、母性行为发作和抗焦虑。这些变化对于后代的健康发展以及母亲的心理健康都是必不可少的。这些适应的干扰，例如慢性压力，可能会增加产后情绪障碍的脆弱性，但潜在的机制尚不清楚。从最初的资金期间的数据表明，慢性妊娠应激（PS）在大鼠母鼠防止这些怀孕和哺乳期相关的adaptation.In延续这些和最近的结果，我们的目标首先是充分表征生殖相关的基因表达模式的改变下丘脑室旁核（一个区域高度参与孕产妇和压力的适应），以及这些基因表达模式是如何改变PS。反过来，药理学操作，或恢复慢性抗抑郁药治疗，神经元靶向通路/系统被确定为改变PS将揭示其因果作用PS诱导的适应不良。这些结果将首次在遗传和细胞水平上重要地增加我们对适应性和适应不良的围产期改变的理解。