title: Maternal Immune Activation and Autism Spectrum Disorder: From Rodents to Nonhuman and Human Primates.
abstract: A subset of women who are exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental or neuropsychiatric disorder. Although epidemiology studies have primarily focused on the association between maternal infection and an increased risk of offspring schizophrenia, mounting evidence indicates that maternal infection may also increase the risk of autism spectrum disorder. A number of factors, including genetic susceptibility, the intensity and timing of the infection, and exposure to additional aversive postnatal events, may influence the extent to which maternal infection alters fetal brain development and which disease phenotype (autism spectrum disorder, schizophrenia, other neurodevelopmental disorders) is expressed. Preclinical animal models provide a test bed to systematically evaluate the effects of maternal infection on fetal brain development, determine the relevance to human central nervous system disorders, and to evaluate novel preventive and therapeutic strategies. Maternal immune activation models in mice, rats, and nonhuman primates suggest that the maternal immune response is the critical link between exposure to infection during pregnancy and subsequent changes in brain and behavioral development of offspring. However, differences in the type, severity, and timing of prenatal immune challenge paired with inconsistencies in behavioral phenotyping approaches have hindered the translation of preclinical results to human studies. Here we highlight the promises and limitations of the maternal immune activation model as a preclinical tool to study prenatal risk factors for autism spectrum disorder, and suggest specific changes to improve reproducibility and maximize translational potential.
authors.affiliation: UC Davis MIND Institute, University of California, Davis, California; Department of Psychiatry and Behavioral Sciences, University of California, Davis, California.
authors.forename: Milo
authors.initials: M
authors.lastname: Careaga
authors.affiliation: UC Davis MIND Institute, University of California, Davis, California; California National Primate Research Center, University of California, Davis, California; Biomarker Group, Drug Development Research Laboratories, Sumitomo Dainippon Pharma Co., Ltd., Osaka, Japan.
authors.forename: Takeshi
authors.initials: T
authors.lastname: Murai
authors.affiliation: UC Davis MIND Institute, University of California, Davis, California; Department of Psychiatry and Behavioral Sciences, University of California, Davis, California; California National Primate Research Center, University of California, Davis, California. Electronic address: mdbauman@ucdavis.edu.
authors.forename: Melissa D
authors.initials: MD
authors.lastname: Bauman
mesh_terms: D000818:Animals; D000067877:Autism Spectrum Disorder / Q000209:etiology / Q000276:immunology*; D001921:Brain / Q000254:growth & development / Q000276:immunology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D008253:Macaca mulatta; D008431:Maternal-Fetal Exchange; D051379:Mice; D011066:Poly C; D011247:Pregnancy; D011251:Pregnancy Complications, Infectious / Q000276:immunology*; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology*; D051381:Rats; D012307:Risk Factors
chemical_list: D011066:Poly C
keywords: Animal model; Autism; Neuroimmunology; Prenatal; Risk factor; Schizophrenia