Neuronal migration disturbance in neurodevelopment disorders: Role of environmental factors

Migration of neurons from the area of their generation to their final destination is a central event in brain development. During development, this process is highly sensitive to the effect produced by the exposure to different environmental factors like pathogenic infections, methylmercury, lead, alcohol, ionizing irradiation and drugs, among other. In fact, it has been established that disturbance of the normal process of the neuronal migration is the major cause of brain malformation, functional abnormalities and some behavioral deficit in both experimental animals and humans. Indeed, an increasing number of studies have suggested that disruption of neuronal migration is involved in the etiology of neurodevelopment disorders (NDDs), like schizophrenia, autism spectrum disorder, attention-deficit/hyperactivity disorder, and dyslexia, as well as cerebral palsy and mental retardation. Although it is not completely defined all causes of neuronal migration disruption and the relationship of these alteration with NDDs, it has been found that patients with these conditions present abnormalities in genes that encode proteins which regulate neuronal migration during development; it has been suggested that the structural, cytoarchitectural and functional brain abnormalities found in these patients might be due, at least partially, to an aberrant neuronal migration process. Among the agents that it is known produce neuronal movement alteration are included different environmental factors, nevertheless, it is not completely defined the role and particularly the molecular mechanisms by which these factors contribute in the etiology of NDDs. In this chapter we review the current knowledge regarding the relationship between neuronal migration and developmental disorders. In particular, we focus on the disruption of neuronal migration induced by different environmental factors (biological, chemical and physical) and the role of these effects as a risk factor for NDDs. Recent advances in the molecular mechanisms of disruption of neuronal migration by environmental factors and their relationship with NDDs will also be reviewed, and how this knowledge may contributing to a better understanding of the physiopathology of NDDs in which neuronal migration disruption is involved.