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Maternal Immune Activation during Pregnancy Alters Postnatal Brain Growth and Cognitive Development in Nonhuman Primate Offspring.
Vlasova, Roza M; Iosif, Ana-Maria; Ryan, Amy M; Funk, Lucy H; Murai, Takeshi; Chen, Shuai; Lesh, Tyler A; Rowland, Douglas J; Bennett, Jeffrey; Hogrefe, Casey E; Maddock, Richard J; Gandal, Michael J; Geschwind, Daniel H; Schumann, Cynthia M; Van de Water, Judy; McAllister, A Kimberley; Carter, Cameron S; Styner, Martin A; Amaral, David G; Bauman, Melissa D.
Afiliación
  • Vlasova RM; Department of Psychiatry, University of North Carolina, Chapel Hill, North Carolina, 27514.
  • Iosif AM; Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Ryan AM; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Funk LH; The MIND Institute, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Murai T; California National Primate Research Center, University of California, Davis, California, 95616.
  • Chen S; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Lesh TA; California National Primate Research Center, University of California, Davis, California, 95616.
  • Rowland DJ; Division of Biostatistics, Department of Public Health Sciences, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Bennett J; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Hogrefe CE; Center for Genomic and Molecular Imaging, University of California, Davis, California, 95616.
  • Maddock RJ; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Gandal MJ; California National Primate Research Center, University of California, Davis, California, 95616.
  • Geschwind DH; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Schumann CM; Neurogenetics Program, Department of Neurology, University of California, Los Angeles, California, 90095.
  • Van de Water J; Neurogenetics Program, Department of Neurology, University of California, Los Angeles, California, 90095.
  • McAllister AK; Department of Psychiatry and Behavioral Sciences, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Carter CS; The MIND Institute, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Styner MA; The MIND Institute, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Amaral DG; Rheumatology/Allergy and Clinical Immunology, School of Medicine, University of California, Davis, Sacramento, California, 95817.
  • Bauman MD; The MIND Institute, School of Medicine, University of California, Davis, Sacramento, California, 95817.
J Neurosci ; 41(48): 9971-9987, 2021 12 01.
Article en En | MEDLINE | ID: mdl-34607967
ABSTRACT
Human epidemiological studies implicate exposure to infection during gestation in the etiology of neurodevelopmental disorders. Animal models of maternal immune activation (MIA) have identified the maternal immune response as the critical link between maternal infection and aberrant offspring brain and behavior development. Here we evaluate neurodevelopment of male rhesus monkeys (Macaca mulatta) born to MIA-treated dams (n = 14) injected with a modified form of the viral mimic polyinosinicpolycytidylic acid at the end of the first trimester. Control dams received saline injections at the same gestational time points (n = 10) or were untreated (n = 4). MIA-treated dams exhibited a strong immune response as indexed by transient increases in sickness behavior, temperature, and inflammatory cytokines. Although offspring born to control or MIA-treated dams did not differ on measures of physical growth and early developmental milestones, the MIA-treated animals exhibited subtle changes in cognitive development and deviated from species-typical brain growth trajectories. Longitudinal MRI revealed significant gray matter volume reductions in the prefrontal and frontal cortices of MIA-treated offspring at 6 months that persisted through the final time point at 45 months along with smaller frontal white matter volumes in MIA-treated animals at 36 and 45 months. These findings provide the first evidence of early postnatal changes in brain development in MIA-exposed nonhuman primates and establish a translationally relevant model system to explore the neurodevelopmental trajectory of risk associated with prenatal immune challenge from birth through late adolescence.SIGNIFICANCE STATEMENT Women exposed to infection during pregnancy have an increased risk of giving birth to a child who will later be diagnosed with a neurodevelopmental disorder. Preclinical maternal immune activation (MIA) models have demonstrated that the effects of maternal infection on fetal brain development are mediated by maternal immune response. Since the majority of MIA models are conducted in rodents, the nonhuman primate provides a unique system to evaluate the MIA hypothesis in a species closely related to humans. Here we report the first longitudinal study conducted in a nonhuman primate MIA model. MIA-exposed offspring demonstrate subtle changes in cognitive development paired with marked reductions in frontal gray and white matter, further supporting the association between prenatal immune challenge and alterations in offspring neurodevelopment.
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Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Complicaciones Infecciosas del Embarazo / Efectos Tardíos de la Exposición Prenatal / Encéfalo / Modelos Animales de Enfermedad / Trastornos del Neurodesarrollo Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Pregnancy Idioma: En Revista: J Neurosci Año: 2021 Tipo del documento: Article

Texto completo: 1 Colección: 01-internacional Banco de datos: MEDLINE Asunto principal: Complicaciones Infecciosas del Embarazo / Efectos Tardíos de la Exposición Prenatal / Encéfalo / Modelos Animales de Enfermedad / Trastornos del Neurodesarrollo Tipo de estudio: Observational_studies / Prognostic_studies / Risk_factors_studies Límite: Animals / Pregnancy Idioma: En Revista: J Neurosci Año: 2021 Tipo del documento: Article