title: Impact of Maternal Stress in Pregnancy on Brain Function of the Offspring.
abstract: Epidemiological studies suggest that exposure to prenatal stressors, including malnutrition, maternal immune activation (MIA), and adverse life events, is associated with increased risks of schizophrenia, autism spectrum disorder (ASD), and attention-deficit hyperactivity disorder (ADHD). However, the underlying pathophysiological mechanisms are unclear. The first trimester of pregnancy is particularly a vulnerable period. During this period, the self-renewal of neural stem cells and neurogenesis vigorously occur, and synaptic connections are partially formed in the telencephalon. Disturbance of this neuronal proliferation and migration during the first trimester may underlie the increased susceptibility to these disorders. Epigenetic modifications, such as DNA methylation and histone modification, are critical mechanisms for regulating gene expression. They can be affected by stress and are associated with an increase in susceptibility to schizophrenia and developmental disabilities. Injection of polyinosinic-polycytidylic acid or lipopolysaccharide induces MIA, enhances the expression of proinflammatory cytokines, and leads to the activation of microglia and the subsequent epigenetic modification of neurons or glia in the offspring. Furthermore, maternal high-fat diet and obesity similarly induce MIA and therefore may increase the risk of developmental disabilities. In addition, maternal stress reprograms the hypothalamic-pituitary-adrenal (HPA) axis, which regulates the stress response in the offspring. Thus, exposure to prenatal stress may increase the susceptibility to schizophrenia, ASD, or ADHD in the offspring through epigenetic modifications, MIA, and alteration of the HPA axis.
authors.affiliation: Division of Anatomy and Cell Biology, Department of Anatomy, Shiga University of Medical Science.
authors.forename: Jun
authors.initials: J
authors.lastname: Udagawa
authors.forename: Kodai
authors.initials: K
authors.lastname: Hino
mesh_terms: D000818:Animals; D001289:Attention Deficit Disorder with Hyperactivity / Q000209:etiology*; D000067877:Autism Spectrum Disorder / Q000209:etiology*; D059305:Diet, High-Fat / Q000009:adverse effects; D004198:Disease Susceptibility; D005260:Female; D006801:Humans; D007030:Hypothalamo-Hypophyseal System / Q000503:physiopathology; D007154:Immune System Diseases / Q000150:complications*; D008016:Life Change Events; D044342:Malnutrition / Q000150:complications*; D018811:Maternal Exposure / Q000009:adverse effects*; D008431:Maternal-Fetal Exchange; D009765:Obesity / Q000150:complications; D010913:Pituitary-Adrenal System / Q000503:physiopathology; D011247:Pregnancy; D011248:Pregnancy Complications; D011297:Prenatal Exposure Delayed Effects / Q000209:etiology*; D012306:Risk; D012559:Schizophrenia / Q000209:etiology*; D013312:Stress, Physiological / Q000502:physiology*; D013315:Stress, Psychological / Q000150:complications*