Understanding the epigenetics of neurodevelopmental disorders and DOHaD.
Understanding the epigenetics of neurodevelopmental disorders and DOHaD.
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DOI：
10.1017/s2040174415000057
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发表时间：
2015-04
影响因子：
1.7
通讯作者：
Takeo Kubota;Kunio Miyake;Natsuyo Hariya;K. Mochizuki
中科院分区：
文献类型：
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作者：
Takeo Kubota;Kunio Miyake;Natsuyo Hariya;K. Mochizuki
健康和疾病的发育起源假说（DOHaD）指的是这样一个概念：“胎儿时期的营养不良会导致胎儿的节俭本性，因此，如果他们在目前营养充足的社会中长大，他们患肥胖症和糖尿病等非传染性疾病的可能性就会更高。”表观遗传学是DNA和组蛋白的化学变化，在不改变DNA序列的情况下影响基因的表达。一些证据表明，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，这种改变的表达可能持续存在，并可能导致代谢紊乱。同样，新生儿期的精神压力可以改变新生儿神经元基因的表观遗传表达状态。此外，这种环境、压力诱导的表观遗传变化通过精子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，表观遗传改变可能与基因表达相反。因此，我们有可能建立“先发制人的医学”，与早期发现异常的表观遗传状态和早期使用表观遗传恢复药物相结合，可以预防与DOHaD相关的疾病的发展。
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.