Grissom Nicola M, Reyes Teresa M
Institute of Translational Medicine and Therapeutics, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Boulevard, Philadelphia, PA 19104, United States.
Int J Dev Neurosci. 2013 Oct;31(6):406-14. doi: 10.1016/j.ijdevneu.2012.11.006. Epub 2012 Nov 28.
The size of an infant at birth, a measure of gestational growth, has been recognized for many years as a biomarker of future risk of morbidity. Both being born small for gestational age (SGA) and being born large for gestational age (LGA), are associated with increased rates of obesity and metabolic disorder, as well as a number of mental disorders including attention deficit/hyperactivity disorder, autism, anxiety, and depression. The common risks raise the question of what neurobiological mechanisms are altered in SGA and LGA offspring. Here we review recent findings allowing for direct comparison of neurobiological outcomes of SGA and LGA in human and animal models. We also present new data highlighting similarities and differences in behavior and neurobiology in our mouse models of SGA and LGA. Overall, there is significant data to support aberrant epigenetic mechanisms, particularly related to DNA methylation, in the brains of SGA and LGA offspring, leading to disruptions in the cell cycle in development and gene expression in adulthood.
出生时婴儿的大小作为衡量孕期生长的指标，多年来一直被视为未来发病风险的生物标志物。小于胎龄儿（SGA）和大于胎龄儿（LGA）出生都与肥胖和代谢紊乱率增加有关，以及与包括注意力缺陷多动障碍、自闭症、焦虑症和抑郁症在内的多种精神障碍有关。这些共同风险引发了一个问题，即SGA和LGA后代的神经生物学机制发生了哪些改变。在这里，我们回顾了最近的研究结果，以便直接比较人类和动物模型中SGA和LGA的神经生物学结果。我们还展示了新的数据，突出了我们的SGA和LGA小鼠模型在行为和神经生物学方面的异同。总体而言，有大量数据支持SGA和LGA后代大脑中异常的表观遗传机制，特别是与DNA甲基化相关的机制，这导致发育过程中的细胞周期和成年期的基因表达受到干扰。
