Impact of prenatal environmental stress on cortical development

Abstract

Prenatal exposure of the developing brain to various types of environmental stress increases susceptibility to neuropsychiatric disorders such as autism, attention deficit hyperactivity disorder and schizophrenia. Given that even subtle perturbations by prenatal environmental stress in the cerebral cortex impair the cognitive and memory functions, this review focuses on underlying molecular mechanisms of pathological cortical development. We especially highlight recent works that utilized animal exposure models, human specimens or/and induced Pluripotent Stem (iPS) cells to demonstrate: (1) molecular mechanisms shared by various types of environmental stressors, (2) the mechanisms by which the affected extracortical tissues indirectly impact the cortical development and function, and (3) interaction between prenatal environmental stress and the genetic predisposition of neuropsychiatric disorders. Finally, we discuss current challenges for achieving a comprehensive understanding of the role of environmentally disturbed molecular expressions in cortical maldevelopment, knowledge of which may eventually facilitate discovery of interventions for prenatal environment-linked neuropsychiatric disorders.

Keywords: alcohol; autism; cortical development; gene-environment interaction; iPS cells; maternal immune activation; prenatal environmental stress; schizophrenia.

Figure 1

HSF1-mediated protection of neural progenitor cells from various types of environmental stress. Upon exposure to environmental stress, HSF1 is activated and HSPs transcribed by HSF1 inhibit cell death. HSF1 also keeps cell cycling/proliferation under stress exposure. The downstream player X is still unknown.

Figure 2

Cell-to-cell variability of HSF1 activation in response to environmental challenges is increased in schizophrenia neural progenitor cells. The number of cells that are in the levels of excess or very little activation of HSF1 was increased in the schizophrenia cells (Hashimoto-Torii et al., ; Brennand et al., 2015). These outlier cells may be at the risk of manifesting pathophysiological features (indicated by the cells surrounded by broken lines).