Multifactorial Origin of Neurodevelopmental Disorders: Approaches to Understanding Complex Etiologies

Toxics

Alessia De Felice²  Laura Ricceri²  Aldina Venerosi²  Flavia Chiarotti²  Gemma Calamandrei¹ 

[1] Unit of Neurotoxicology and Neuroendocrinology, Department of Cell Biology and Neurosciences, Istituto Superiore di Sanità, Viale Regina Elena 299, I-00161 Roma, Italy;

关键词: developmental neurotoxicity;    autism spectrum disorders;    attention deficit hyperactivity disorder;    methylmercury;    organophosphate pesticides;    single nucleotide polymorphisms;    maternal stress;    exposome;    biomarkers;    rodents;   

DOI  :  10.3390/toxics3010089

来源: mdpi

【 摘 要 】

A significant body of evidence supports the multifactorial etiology of neurodevelopmental disorders (NDDs) affecting children. The present review focuses on early exposure to environmental chemicals as a risk factor for neurodevelopment, and presents the major lines of evidence derived from epidemiological studies, underlying key uncertainties and research needs in this field. We introduce the exposome concept that, encompassing the totality of human environmental exposures to multiple risk factors, aims at explaining individual vulnerability and resilience to early chemical exposure. In this framework, we synthetically review the role of variable gene backgrounds, the involvement of epigenetic mechanisms as well as the function played by potential effect modifiers such as socioeconomic status. We describe laboratory rodent studies where the neurodevelopmental effects of environmental chemicals are assessed in the presence of either a “vulnerable” gene background or adverse pregnancy conditions (i.e., maternal stress). Finally, we discuss the need for more descriptive and “lifelike” experimental models of NDDs, to identify candidate biomarkers and pinpoint susceptible groups or life stages to be translated to large prospective studies within the exposome framework.

【 授权许可】

CC BY   
© 2015 by the authors; licensee MDPI, Basel, Switzerland.