Cited by 261Neurogenesis and neuroplasticity mechanismsAutism Spectrum Disorder ResearchInfectious Encephalopathies and Encephalitis

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Prenatal Viral Infection Leads to Pyramidal Cell Atrophy and Macrocephaly in Adulthood: Implications for Genesis of Autism and Schizophrenia

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Fatemi, S. Hossein, Earle, Julie, Kanodia, Reena, Kist, David, Emamian, Effat S., Patterson, Paul H., Shi, Limin, Sidwell, Robert·2002·Cellular and Molecular Neurobiology

DOI 10.1023/a:1015337611258PMC PMC11533729

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Abstract

We investigated the role of maternal exposure to human influenza virus (H1N1) in C57BL/6 mice on Day 9 of pregnancy on pyramidal and nonpyramidal cell density, pyramidal nuclear area, and overall brain size in Day 0 neonates and 14-week-old progeny and compared them to sham-infected cohorts. Pyramidal cell density increased significantly (p < 0.0038) by 170% in Day 0 infected mice vs. controls. Nonpyramidal cell density decreased by 33% in Day 0 infected progeny vs. controls albeit, nonsignificantly. Pyramidal cell nuclear size decreased significantly (p < 0.0465) by 29% in exposed newborn mice vs. controls. Fourteen-week-old exposed mice continued to show significant increases in both pyramidal and nonpyramidal cell density values vs. controls respectively (p < 0.0085 E1 (exposed group 1), p < 0.0279 E2 (exposed group 2) pyramidal cell density; p < 0.0092 E1, p < 0.0252 E2, nonpyramidal cell density). By the same token, pyramidal cell nuclear size exhibited 37-43% reductions when compared to control values; these were statistically significant vs. controls (p < 0.04 E1, p < 0.0259 E2). Brain and ventricular area measurements in adult exposed mice also showed significant increases and decreases respectively vs. controls. Ventricular brain ratios exhibited 38-50% decreases in exposed mice vs. controls. While the rate of pyramidal cell proliferation per unit area decreased from birth to adulthood in both control and exposed groups, nonpyramidal cell growth rate increased only in the exposed adult mice. These data show for the first time that prenatal exposure of pregnant mice on Day 9 of pregnancy to a sublethal intranasal administration of influenza virus has both short-term and long-lasting deleterious effects on developing brain structure in the progeny as evident by altered pyramidal and nonpyramidal cell density values; atrophy of pyramidal cells despite normal cell proliferation rate and final enlargement of brain. Moreover, abnormal corticogenesis is associated with development of abnormal behavior in the exposed adult mice.

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Authors: Fatemi, S. H., Earle, J., Kanodia, R., Kist, D., Emamian, E. S., Patterson, P. H., Shi, L., & Sidwell, R.
Affiliations: University of Minnesota (US)
California Institute of Technology (US)
Utah State University (US)
Corresponding author: Fatemi, S. Hossein
ORCID: Fatemi, S. Hossein
Patterson, Paul H.
Shi, Limin
Venue: Cellular and Molecular Neurobiology
Publisher: Springer Science and Business Media LLC
Published: 2002-02
Volume: 22
Issue: 1
Pages: 25-33
ISSN: 0272-4340 (ISSN-L)
1573-6830
DOI: 10.1023/a:1015337611258
PMC: PMC11533729
OpenAlex: W1549834980
Cited by: 261
References: 26
Citations by year: 2026: 1 · 2025: 3 · 2024: 6 · 2023: 3 · 2022: 9 · 2021: 6 · 2020: 5 · 2019: 5 · 2018: 10 · 2017: 5 · 2016: 7 · 2015: 19 · 2014: 11 · 2013: 14 · 2012: 15
FWCI: 2.86
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Licence: www.springernature.com/gp/researchers/text-and-data-mining (tdm)
www.springernature.com/gp/researchers/text-and-data-mining (vor)
Locations: Cellular and Molecular Neurobiology (publishedVersion)
PubMed Central (publishedVersion)
PubMed (publishedVersion)
CaltechAUTHORS (California Institute of Technology) (submittedVersion)
Funders: U.S. Public Health Service (I-A165291)
Topics: Life Sciences › Neuroscience › Developmental Neuroscience › Neurogenesis and neuroplasticity mechanisms
Life Sciences › Neuroscience › Cognitive Neuroscience › Autism Spectrum Disorder Research
Health Sciences › Medicine › Infectious Diseases › Infectious Encephalopathies and Encephalitis
Keywords: prenatal viral infection, H1N1 influenza, maternal infection, macrocephaly, autism spectrum disorder, schizophrenia, cortical development, brain size, ventriculomegaly, neuronal proliferation, C57BL/6 mice, brain development
MeSH terms: Aging, Animals, Atrophy, Autistic Disorder, Brain, Female, Mice, Inbred C57BL, Orthomyxoviridae Infections, Influenza A virus, Pregnancy, Pregnancy Complications, Infectious, Schizophrenia, Pyramidal Cells, Mice

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Prenatal Viral Infection Leads to Pyramidal Cell Atrophy and Macrocephaly in Adulthood: Implications for Genesis of Autism and Schizophrenia

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