title: Prenatal immune challenge compromises the normal course of neurogenesis during development of the mouse cerebral cortex.
abstract: Maternal infection during pregnancy is an environmental risk factor for the development of severe brain disorders in offspring, including schizophrenia and autism. However, little is known about the neurodevelopmental mechanisms underlying the association between prenatal exposure to infection and the emergence of cognitive and behavioral dysfunctions in later life. By injecting viral mimetic polyriboinosinic-polyribocytidylic acid (Poly I:C) into mice, we investigated the influence of maternal immune challenge during pregnancy on the development of the cerebral cortex of offspring. Our previous study showed that stimulation of the maternal immune system compromised the expression properties of transcription factors and the synaptogenesis of cortical neurons in upper layers but not those in deeper layers. The objective of the current study was to examine further whether maternal immune challenge has an influence on the cellular-biological features of the cortical progenitors that generate distinct cortical neuronal subtypes. We found the following abnormalities in the cortex of mice given the prenatal Poly I:C injection during later stages of cortical neurogenesis. First, proliferative activity and the expression of Pax6, which is a master regulator of the gene expression of transcription factors, were significantly decreased in the cortical progenitors. Second, the laminar allocation and gene expression were significantly altered in the daughter neurons generated at the same birth dates. These results demonstrate that specific abnormalities in the cortical progenitors preceded deficits in neuronal phenotypes. These changes may underlie the emergence of psychiatric brain and behavioral dysfunctions after in utero exposure to an infection.
authors: Laboratory of Molecular Biology, Department of Biofunctional Analysis, Gifu Pharmaceutical University, Gifu, Japan.
authors: Hitomi
authors: H
authors: Soumiya
authors: Hidefumi
authors: H
authors: Fukumitsu
authors: Shoei
authors: S
authors: Furukawa
mesh_terms: D000818:Animals; D021461:Animals, Outbred Strains; D020274:Autoimmune Diseases of the Nervous System / Q000139:chemically induced / Q000276:immunology* / Q000473:pathology; D002540:Cerebral Cortex / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D005260:Female; D008297:Male; D051379:Mice; D009421:Nervous System Malformations / Q000276:immunology* / Q000473:pathology* / Q000821:virology; D055495:Neurogenesis / Q000276:immunology*; D011070:Poly I-C / Q000633:toxicity; D011247:Pregnancy; D011297:Prenatal Exposure Delayed Effects / Q000276:immunology* / Q000473:pathology* / Q000821:virology
chemical_list: D011070:Poly I-C