Grova Nathalie, Schroeder Henri, Olivier Jean-Luc, Turner Jonathan D
Immune Endocrine Epigenetics Research Group, Department of Infection and Immunity, Luxembourg Institute of Health, 29 rue Henri Koch, L-4354 Esch-sur-Alzette, Luxembourg.
Calbinotox, Faculty of Science and Technology, Lorraine University, Campus Aiguillettes, B.P. 70239, 54506 Vandoeuvre-lès-Nancy, France.
Int J Genomics. 2019 Jan 14;2019:2085496. doi: 10.1155/2019/2085496. eCollection 2019.
The incidence of neurodevelopmental and neurodegenerative diseases worldwide has dramatically increased over the last decades. Although the aetiology remains uncertain, evidence is now growing that exposure to persistent organic pollutants during sensitive neurodevelopmental periods such as early life may be a strong risk factor, predisposing the individual to disease development later in life. Epidemiological studies have associated environmentally persistent organic pollutant exposure to brain disorders including neuropathies, cognitive, motor, and sensory impairments; neurodevelopmental disorders such as autism spectrum disorder (ASD) and attention-deficit hyperactivity disorder (ADHD); and neurodegenerative diseases including Alzheimer's disease, Parkinson's disease, and amyotrophic lateral sclerosis (ALS). In many ways, this expands the classical "Developmental Origins of Health and Disease" paradigm to include exposure to pollutants. This model has been refined over the years to give the current "three-hit" model that considers the individual's genetic factors as a first "hit." It has an immediate interaction with the early-life exposome (including persistent organic pollutants) that can be considered to be a second "hit." Together, these first two "hits" produce a quiescent or latent phenotype, most probably encoded in the epigenome, which has become susceptible to a third environmental "hit" in later life. It is only after the third "hit" that the increased risk of disease symptoms is crystallised. However, if the individual is exposed to a different environment in later life, they would be expected to remain healthy. In this review, we examine the effect of exposure to persistent organic pollutants and particulate matters in early life and the relationship to subsequent neurodevelopmental and neurodegenerative disorders. The roles of those environmental factors which may affect epigenetic DNA methylation and therefore influence normal neurodevelopment are then evaluated.
在过去几十年中，全球神经发育和神经退行性疾病的发病率急剧上升。尽管病因仍不明确，但现在越来越多的证据表明，在生命早期等敏感的神经发育阶段接触持久性有机污染物可能是一个强大的风险因素，使个体在晚年易患疾病。流行病学研究已将环境持久性有机污染物暴露与多种脑部疾病联系起来，包括神经病变、认知、运动和感觉障碍；神经发育障碍，如自闭症谱系障碍（ASD）和注意力缺陷多动障碍（ADHD）；以及神经退行性疾病，包括阿尔茨海默病、帕金森病和肌萎缩侧索硬化症（ALS）。从很多方面来看，这将经典的“健康与疾病的发育起源”范式扩展到了包括污染物暴露在内的情况。多年来，这个模型已经得到完善，形成了当前的“三击”模型，该模型将个体的遗传因素视为第一次“打击”。它与生命早期的暴露组（包括持久性有机污染物）立即相互作用，这可被视为第二次“打击”。这前两次“打击”共同产生一种静止或潜在的表型，很可能编码在表观基因组中，这种表型在晚年易受到第三次环境“打击”。只有在第三次“打击”之后，疾病症状增加的风险才会显现出来。然而，如果个体在晚年接触到不同的环境，他们预计仍会保持健康。在这篇综述中，我们研究了生命早期接触持久性有机污染物和颗粒物的影响以及与随后的神经发育和神经退行性疾病的关系。然后评估那些可能影响表观遗传DNA甲基化从而影响正常神经发育的环境因素的作用。
