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啮齿动物产后母性护理的神经发育后遗症:分子见解的临床与研究意义

Neurodevelopmental sequelae of postnatal maternal care in rodents: clinical and research implications of molecular insights.

作者信息

Kaffman Arie, Meaney Michael J

机构信息

Abraham Ribicoff Labs, Department of Psychiatry, Yale University School of Medicine, New Haven, CT 06598, USA.

出版信息

J Child Psychol Psychiatry. 2007 Mar-Apr;48(3-4):224-44. doi: 10.1111/j.1469-7610.2007.01730.x.

Abstract

Parental care plays an important role in the emotional and cognitive development of the offspring. Children who have been exposed to abuse or neglect are more likely to develop numerous psychopathologies, while good parent-infant bonding is associated with improved resiliency to stress. Similar observations have also been reported in non-human primates and rodents, suggesting that at least some neurodevelopmental aspects of parent-offspring interactions are conserved among mammals and could therefore be studied in animals. We present data to suggest that frequency of licking and grooming provided by the dam during a critical period in development plays an important role in modifying neurodevelopment. These findings are examined in the broader context in which exposure to other sensory modalities such as vision or hearing during a specific period in development shapes brain development with functional consequences that persist into adulthood. We also discuss recent rodent work showing that increased frequency of licking and grooming provided by the dam during the first week of life is associated with changes in DNA methylation of promoter elements that control expression of these genes and behavior. The stability of DNA methylation in postmitotic cells provides a possible molecular scaffold by which changes in gene expression and behavioral traits induced by postnatal maternal care are maintained throughout life. Finally, the relevance of findings reported in rodents to those noted in non-human primates and humans are assessed and the research and clinical implications of these observations for future work are explored.

摘要

亲代抚育在后代的情感和认知发展中起着重要作用。遭受虐待或忽视的儿童更有可能出现多种精神病理学问题,而良好的亲子关系则与增强的应激恢复力相关。在非人类灵长类动物和啮齿动物中也有类似的观察结果,这表明亲子互动的至少一些神经发育方面在哺乳动物中是保守的,因此可以在动物身上进行研究。我们提供的数据表明,在发育的关键时期,母鼠提供的舔舐和梳理频率在改变神经发育方面起着重要作用。这些发现是在更广泛的背景下进行研究的,即在发育的特定时期接触其他感觉模式(如视觉或听觉)会塑造大脑发育,并产生持续到成年期的功能后果。我们还讨论了最近关于啮齿动物的研究,该研究表明,在出生后第一周,母鼠增加舔舐和梳理的频率与控制这些基因表达和行为的启动子元件的DNA甲基化变化有关。有丝分裂后细胞中DNA甲基化的稳定性提供了一种可能的分子支架,通过它,出生后母性照料诱导的基因表达和行为特征的变化得以终生维持。最后,评估了啮齿动物研究结果与非人类灵长类动物和人类研究结果的相关性,并探讨了这些观察结果对未来研究和临床工作的意义。

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