Prenatal viral infection leads to pyramidal cell atrophy and macrocephaly in adulthood: Implications for genesis of autism and schizophrenia

S. Hossein Fatemi, Julie Earle, Reena Kanodia, David Kist, Effat S. Emamian, Paul H. Patterson, Limin Shi, Robert Sidwell

Research output: Contribution to journalArticlepeer-review

232 Scopus citations


We investigated the role of maternal exposure to human influenza virus (H1N1) in C57BL/6 mice on Day 9 of pregnancy on pyramidal and on pyramidal 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 El, 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.

Original languageEnglish (US)
Pages (from-to)25-33
Number of pages9
JournalCellular and Molecular Neurobiology
Issue number1
StatePublished - 2002

Bibliographical note

Funding Information:
We are grateful to NARSAD, the Minnesota Medical Foundation, and the Stanley Scholar program (Dr. S. C. Schulz) for provision of funds to carry out this project. S. Hossein Fatemi is an established Phyllis and Perry Schwartz NARSAD investigator. R. Sidwell was supported by NIAID contract No. I-A165291. Paul H. Patterson was supported by Ginger and Ted Jenkins, and the Mettler Autism Fund. We are grateful for careful secretarial help provided by Ms Janet Holland.


  • Autism
  • Human influenza virus
  • Macrocephaly
  • Prenatal exposure
  • Pyramidal cell atrophy
  • Schizophrenia


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