Maussion Gilles, Demirova Iveta, Gorwood Philip, Ramoz Nicolas
Montreal Neurological Institute and Hospital, McGill University, Montreal, QC, Canada.
INSERM U1266, Institute of Psychiatry and Neuroscience of Paris, Paris, France.
Front Nutr. 2019 Aug 13;6:118. doi: 10.3389/fnut.2019.00118. eCollection 2019.
Anorexia nervosa (AN) is a dramatic psychiatric disorder characterized by dysregulations in food intake and reward processing, involving molecular and cellular changes in several peripheral cell types and central neuronal networks. Genomic and epigenomic analyses have allowed the identification of multiple genetic and epigenetic modifications highlighting the complex pathophysiology of AN. Behavioral and genetic rodent models have been used to recapitulate and investigate, with some limitations, the cellular and molecular changes that potentially underlie eating disorders. In the last 5 years, the use of induced pluripotent stem cells (IPSCs), combined with CRISPR-Cas9 technology, has led to the generation of specific neuronal cell subtypes engineered from human somatic samples, representing a powerful tool to complement observations made in human samples and data collected from animal models. Systems biology using IPSCs has indeed proved to be a valuable approach for the study of metabolic disorders, in addition to neurodevelopmental and psychiatric disorders. The manuscript, while reviewing the main findings related to the genetic, epigenetic, and cellular bases of AN, will present how new studies published, or to be performed, in the field of IPSC-derived cells should improve our current understanding of the pathophysiology of AN and provide potential therapeutic strategies addressing specific endophenotypes.
神经性厌食症（AN）是一种严重的精神疾病，其特征在于食物摄入和奖赏处理失调，涉及多种外周细胞类型和中枢神经网络中的分子和细胞变化。基因组和表观基因组分析已使人们能够识别出多种遗传和表观遗传修饰，凸显了AN复杂的病理生理学。行为和遗传啮齿动物模型已被用于概括和研究饮食失调潜在的细胞和分子变化，但存在一些局限性。在过去5年中，诱导多能干细胞（iPSC）与CRISPR-Cas9技术相结合，已从人类体细胞样本中生成了特定的神经元细胞亚型，这是一种强大的工具，可补充在人类样本中所做的观察以及从动物模型收集的数据。除了神经发育和精神疾病外，使用iPSC的系统生物学已被证明是研究代谢紊乱的一种有价值的方法。本文在回顾与AN的遗传、表观遗传和细胞基础相关的主要发现时，将介绍在iPSC衍生细胞领域已发表或即将开展的新研究应如何增进我们目前对AN病理生理学的理解，并提供针对特定内表型的潜在治疗策略。
