title: Effects of early or late prenatal immune activation in mice on behavioral and neuroanatomical abnormalities relevant to schizophrenia in the adulthood.
abstract: Maternal immune activation (MIA) during pregnancy in rodents increases the risk of the offspring to develop schizophrenia-related behaviors, suggesting a relationship between the immune system and the brain development. Here we tested the hypothesis that MIA induced by the viral mimetic polyinosinic-polycytidylic acid (poly I:C) in early or late gestation of mice leads to behavioral and neuroanatomical disorders in the adulthood. On gestational days (GDs) 9 or 17 pregnant dams were treated with poly I:C or saline via intravenous route and the offspring behaviors were measured during adulthood. Considering the progressive structural neuroanatomical alterations in the brain of individuals with schizophrenia, we used magnetic resonance imaging (MRI) to perform brain morphometric analysis of the offspring aged one year. MIA on GD9 or GD17 led to increased basal locomotor activity, enhanced motor responses to ketamine, a psychotomimetic drug, and reduced time spent in the center of the arena, suggesting an increased anxiety-like behavior. In addition, MIA on GD17 reduced glucose preference in the offspring. None of the treatments altered the relative volume of the lateral ventricles. However, a decrease in brain volume, especially for posterior structures, was observed for one-year-old animals treated with poly I:C compared with control groups. Thus, activation of the maternal immune system at different GDs lead to neuroanatomical and behavioral alterations possibly related to the positive and negative symptoms of schizophrenia. These results provide insights on neuroimmunonological and neurodevelopmental aspects of certain psychopathologies, such as schizophrenia.
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Vivian T
authors.initials: VT
authors.lastname: da Silveira
authors.affiliation: Center for Technology and Research in Magneto-Resonance (CTPMAG), Graduate Program in Electrical Engineering - Universidade Federal de Minas Gerais, Brazil.
authors.forename: Daniel de Castro
authors.initials: DC
authors.lastname: Medeiros
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Jivago
authors.initials: J
authors.lastname: Ropke
authors.affiliation: Center for Technology and Research in Magneto-Resonance (CTPMAG), Graduate Program in Electrical Engineering - Universidade Federal de Minas Gerais, Brazil.
authors.forename: Patricia A
authors.initials: PA
authors.lastname: Guidine
authors.affiliation: Center for Technology and Research in Magneto-Resonance (CTPMAG), Graduate Program in Electrical Engineering - Universidade Federal de Minas Gerais, Brazil.
authors.forename: Gustavo H
authors.initials: GH
authors.lastname: Rezende
authors.affiliation: Center for Technology and Research in Magneto-Resonance (CTPMAG), Graduate Program in Electrical Engineering - Universidade Federal de Minas Gerais, Brazil.
authors.forename: Marcio Flavio D
authors.initials: MF
authors.lastname: Moraes
authors.affiliation: Center for Technology and Research in Magneto-Resonance (CTPMAG), Graduate Program in Electrical Engineering - Universidade Federal de Minas Gerais, Brazil.
authors.forename: Eduardo Mazoni A M
authors.initials: EM
authors.lastname: Mendes
authors.affiliation: Drug Research and Development Center, Department of Physiology and Pharmacology, Medical School, Universidade Federal do Ceará, Brazil.
authors.forename: Danielle
authors.initials: D
authors.lastname: Macedo
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil.
authors.forename: Fabricio A
authors.initials: FA
authors.lastname: Moreira
authors.affiliation: Department of Pharmacology, Institute of Biological Sciences, Universidade Federal de Minas Gerais, Brazil. Electronic address: antoniooliveira@icb.ufmg.br.
authors.forename: Antonio Carlos P
authors.initials: AC
authors.lastname: de Oliveira
mesh_terms: D000367:Age Factors; D000704:Analysis of Variance; D000818:Animals; D000831:Animals, Newborn; D001921:Brain / Q000000981:diagnostic imaging / Q000196:embryology / Q000254:growth & development / Q000473:pathology*; D004195:Disease Models, Animal; D004622:Embryo, Mammalian; D005260:Female; D005518:Food Preferences; D007369:Interferon Inducers / Q000633:toxicity; D007649:Ketamine / Q000633:toxicity; D008124:Locomotion / Q000502:physiology; D008279:Magnetic Resonance Imaging; D001523:Mental Disorders / Q000209:etiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000503:physiopathology*; D012559:Schizophrenia / Q000150:complications* / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology*; D013395:Sucrose / Q000008:administration & dosage
chemical_list: D007369:Interferon Inducers; D013395:Sucrose; D007649:Ketamine; D011070:Poly I-C
keywords: Magnetic resonance imaging; Neurodevelopment; Poly I:C; Prenatal immune activation; Schizophrenia