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Maternal Immune Activation Alters Fetal Brain Development and Enhances Proliferation of Neural Precursor Cells in Rats.
Baines, Kelly J; Hillier, Dendra M; Haddad, Faraj L; Rajakumar, Nagalingam; Schmid, Susanne; Renaud, Stephen J.
Afiliação
  • Baines KJ; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
  • Hillier DM; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
  • Haddad FL; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
  • Rajakumar N; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
  • Schmid S; Department of Psychiatry, University of Western Ontario, London, ON, Canada.
  • Renaud SJ; Department of Anatomy and Cell Biology, Schulich School of Medicine and Dentistry, University of Western Ontario, London, ON, Canada.
Front Immunol ; 11: 1145, 2020.
Article em En | MEDLINE | ID: mdl-32582210
Maternal immune activation (MIA) caused by exposure to pathogens or inflammation during critical periods of neurodevelopment is a major risk factor for behavioral deficits and psychiatric illness in offspring. A spectrum of behavioral abnormalities can be recapitulated in rodents by inducing MIA using the viral mimetic, PolyI:C. Many studies have focused on long-term changes in brain structure and behavioral outcomes in offspring following maternal PolyI:C exposure, but acute changes in prenatal development are not well-characterized. Using RNA-Sequencing, we profiled acute transcriptomic changes in rat conceptuses (decidua along with nascent embryo and placenta) after maternal PolyI:C exposure during early gestation, which enabled us to capture gene expression changes provoked by MIA inclusive to the embryonic milieu. We identified a robust increase in expression of genes related to antiviral inflammation following maternal PolyI:C exposure, and a corresponding decrease in transcripts associated with nervous system development. At mid-gestation, regions of the developing cortex were thicker in fetuses prenatally challenged with PolyI:C, with females displaying a thicker ventricular zone and males a thicker cortical mantle. Along these lines, neural precursor cells (NPCs) isolated from fetal brains prenatally challenged with PolyI:C exhibited a higher rate of self-renewal. Expression of Notch1 and the Notch ligand, delta-like ligand 1, which are both highly implicated in maintenance of NPCs and nervous system development, was increased following PolyI:C exposure. These results suggest that MIA elicits rapid gene expression changes within the conceptus, including repression of neurodevelopmental pathways, resulting in profound alterations in fetal brain development.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Efeitos Tardios da Exposição Pré-Natal / Encéfalo / Desenvolvimento Fetal / Células-Tronco Neurais / Feto / Inflamação Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Pregnancy Idioma: En Revista: Front Immunol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Canadá País de publicação: Suíça

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Efeitos Tardios da Exposição Pré-Natal / Encéfalo / Desenvolvimento Fetal / Células-Tronco Neurais / Feto / Inflamação Tipo de estudo: Prognostic_studies / Risk_factors_studies Limite: Animals / Pregnancy Idioma: En Revista: Front Immunol Ano de publicação: 2020 Tipo de documento: Article País de afiliação: Canadá País de publicação: Suíça