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了解神经发育障碍和发育起源健康与疾病的表观遗传学。

Understanding the epigenetics of neurodevelopmental disorders and DOHaD.

作者信息

Kubota T, Miyake K, Hariya N, Mochizuki K

机构信息

1Department of Epigenetic Medicine, Faculty of Medicine,University of Yamanashi,Chuo,Japan.

2Department of Local Produce and Food Sciences, Faculty of Life and Environmental Sciences, Faculty of Medicine,University of Yamanashi,Kofu,Japan.

出版信息

J Dev Orig Health Dis. 2015 Apr;6(2):96-104. doi: 10.1017/S2040174415000057. Epub 2015 Feb 24.

Abstract

The Developmental Origins of Health and Disease (DOHaD) hypothesis refers to the concept that 'malnutrition during the fetal period induces a nature of thrift in fetuses, such that they have a higher change of developing non-communicable diseases, such as obesity and diabetes, if they grow up in the current well-fed society.' Epigenetics is a chemical change in DNA and histones that affects how genes are expressed without alterations of DNA sequences. Several lines of evidence suggest that malnutrition during the fetal period alters the epigenetic expression status of metabolic genes in the fetus and that this altered expression can persist, and possibly lead to metabolic disorders. Similarly, mental stress during the neonatal period can alter the epigenetic expression status of neuronal genes in neonates. Moreover, such environmental, stress-induced, epigenetic changes are transmitted to the next generation via an acquired epigenetic status in sperm. The advantage of epigenetic modifications over changes in genetic sequences is their potential reversibility; thus, epigenetic alterations are potentially reversed with gene expression. Therefore, we potentially establish 'preemptive medicine,' that, in combination with early detection of abnormal epigenetic status and early administration of epigenetic-restoring drugs may prevent the development of disorders associated with the DOHaD.

摘要

健康与疾病的发育起源(DOHaD)假说指的是这样一种概念:“胎儿期营养不良会使胎儿形成一种节俭的特性,以至于如果他们在当前营养充足的社会中成长,患肥胖症和糖尿病等非传染性疾病的几率会更高。”表观遗传学是DNA和组蛋白中的一种化学变化,它会影响基因的表达方式,而不改变DNA序列。有几条证据表明,胎儿期营养不良会改变胎儿代谢基因的表观遗传表达状态,而且这种改变后的表达可能会持续,并可能导致代谢紊乱。同样,新生儿期的精神压力会改变新生儿神经元基因的表观遗传表达状态。此外,这种由环境压力引起的表观遗传变化会通过精子中获得的表观遗传状态传递给下一代。表观遗传修饰相对于基因序列变化的优势在于其潜在的可逆性;因此,表观遗传改变可能会随着基因表达而逆转。因此,我们有可能建立“预防医学”,即结合早期检测异常的表观遗传状态和早期给予表观遗传恢复药物,可能预防与DOHaD相关疾病的发生。

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