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. © 2011 Wiley‐Liss, Inc.
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Gene expression alterations in MIA also involve neuronal migration processes that could underlie observed cortical layering defects, characterized by a 24% increase in neuron numbers in cortical layers II/III.
“Gene expression alterations also involve neuronal migration processes [128] that could underlie observed cortical layering defects, characterized by a 24% increase in neuron numbers in cortical layers II/III [131].”
From The ASD Living Biology: from cell proliferation to clinical phenotype (2019) · cites this paper as [131]
MIA alters proliferation of cortical neural progenitor cells, laminar allocation of neurons, increased cortical thickness, increased cell density and patches of cortical dysplasia.
“MIA alters proliferation of cortical neural progenitor cells, laminar allocation of neurons, increased cortical thickness, increased cell density and patches of cortical dysplasia.32, 38, 42”
From Maternal immune activation dysregulation of the fetal brain transcriptome and relevance to the pathophysiology of autism spectrum disorder (2018) · cites this paper as [42]
MIA mice have delayed cell development in the neocortex and reduced cell density and abnormal developmental migration in the cerebellum.
“MIA mice have delayed cell development in the neocortex [333] and reduced cell density and abnormal developmental migration in the cerebellum [325].”
From Autism spectrum disorder: neuropathology and animal models (2017) · cites this paper as [333]
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- Authors
- Soumiya, H., Fukumitsu, H., & Furukawa, S.
- Affiliations
- Gifu Pharmaceutical University (JP)
- Corresponding author
- Fukumitsu, Hidefumi
- Furukawa, Shoei
- ORCID
- Fukumitsu, Hidefumi
- Venue
- Journal of Neuroscience Research
- Publisher
- Wiley
- Published
- 2011-07-05
- Volume
- 89
- Issue
- 10
- Pages
- 1575-1585
- ISSN
- 0360-4012 (ISSN-L)
- 1097-4547
- OpenAlex
- W2030695586
- Cited by
- 58
- References
- 61
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 3 · 2021: 2 · 2020: 3 · 2019: 2 · 2018: 4 · 2017: 5 · 2016: 4 · 2015: 4 · 2014: 4 · 2013: 12 · 2012: 9
- FWCI
- 2.72
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Journal of Neuroscience Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
- Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
- Life Sciences › Neuroscience › Biological Psychiatry › Tryptophan and brain disorders
- Keywords
- prenatal immune challenge, maternal infection, cortical development, cortical neurogenesis, cortical progenitors, Pax6, cortical lamination, neuronal cell types, poly(I:C), schizophrenia, autism spectrum disorder, synaptogenesis
- MeSH terms
- Animals, Cerebral Cortex, Female, Male, Nervous System Malformations, Poly I-C, Pregnancy, Prenatal Exposure Delayed Effects, Autoimmune Diseases of the Nervous System, Animals, Outbred Strains, Mice, Neurogenesis
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