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Using Animal Models to Disentangle the Role of Genetic, Epigenetic, and Environmental Influences on Behavioral Outcomes Associated with Maternal Anxiety and Depression

机译:使用动物模型来解开遗传,表观遗传和环境影响对与母亲焦虑和抑郁相关的行为结果的作用

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摘要

The etiology of complex psychiatric disorders results from both genetics and the environment. No definitive environmental factor has been implicated, but studies suggest that deficits in maternal care and bonding may be an important contributing factor in the development of anxiety and depression. Perinatal mood disorders such as postpartum depression occur in approximately 10% of pregnant women and can result in detriments in infant care and bonding. The consequences of impaired maternal–infant attachment during critical early brain development may lead to adverse effects on socioemotional and neurocognitive development in infants resulting in long-term behavioral and emotional problems, including increased vulnerability for mental illness. The exact mechanisms by which environmental stressors such as poor maternal care increase the risk for psychiatric disorders are not known and studies in humans have proven challenging. Two inbred mouse strains may prove useful for studying the interaction between maternal care and mood disorders. BALB/c (BALB) mice are considered an anxious strain in comparison to C57BL/6 (B6) mice in behavioral models of anxiety. These strain differences are most often attributed to genetics but may also be due to environment and gene by environment interactions. For example, BALB mice are described as poor mothers and B6 mice as good mothers and mothering behavior in rodents has been reported to affect both anxiety and stress behaviors in offspring. Changes in gene methylation patterns in response to maternal care have also been reported, providing evidence for epigenetic mechanisms. Characterization of these two mouse inbred strains over the course of pregnancy and in the postpartum period for behavioral and neuroendocrine changes may provide useful information by which to inform human studies, leading to advances in our understanding of the etiology of anxiety and depression and the role of genetics and the environment.
机译:复杂的精神疾病的病因来自遗传学和环境。没有明确的环境因素参与其中,但研究表明,产妇护理和结合能力不足可能是焦虑和抑郁症发展的重要因素。围产期情绪障碍,例如产后抑郁症,约有10%的孕妇发生,并可能损害婴儿护理和粘接。关键的早期大脑发育过程中母婴依恋受损的后果可能导致对婴儿的社会情感和神经认知发育的不利影响,从而导致长期的行为和情感问题,包括精神疾病的易感性增加。尚不清楚环境压力源(如孕产妇护理不佳)增加精神病风险的确切机制,并且对人类的研究已证明具有挑战性。两种近交小鼠品系可能被证明对研究孕产妇保健和情绪障碍之间的相互作用有用。在焦虑行为模型中,与C57BL / 6(B6)小鼠相比,BALB / c(BALB)小鼠被认为是焦虑株。这些菌株差异最常见的是遗传因素,也可能是由于环境和环境相互作用所致。例如,BALB小鼠被描述为贫穷的母亲,B6小鼠被描述为良好的母亲,据报道,啮齿动物的母亲行为会影响后代的焦虑和应激行为。也已经报道了响应孕产妇护理的基因甲基化模式的变化,为表观遗传机制提供了证据。这两种小鼠近交系在妊娠过程中和产后行为和神经内分泌变化的表征可能会提供有用的信息,从而为人类研究提供信息,从而使我们对焦虑和抑郁的病因学及其作用的认识有了新的进展。遗传学和环境。

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