Human influenza viral infection in utero alters glial fibrillary acidic protein immunoreactivity in the developing brains of neonatal mice

S H Fatemi, E. S. Emamian, R. W. Sidwell, D. A. Kist, J. M. Stary, J. A. Earle, P. Thuras

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96 Scopus citations

Abstract

Epidemiological reports describe a strong association between prenatal human influenza viral infection and later development of schizophrenia. Postmodern human brain studies, however, indicate a lack of gliosis in schizophrenic brains presumably secondary to absence of glial cells during the second trimester viral infection in utero. We hypothesized that human influenza infection in day 9 pregnant mice would alter the expression of glial fibrillary acidic protein (GFAP, an important marker of gliosis, neuron migration, and reactive injury) in developing brains of postnatal days 0, 14 and 35 mice. Determination of cellular GFAP immunoreactivity (IR) expressed as cell density in cortex and hippocampus of control and experimental brains showed increases in GFAP-positive density in exposed cortical (P = 0.03 day 14 vs control) and hippocampal cells (P= 0.035 day 14, P= 0.034 day 35). Similarly, ependymal cell layer GFAP-IR cell counts showed increases with increasing brain age from day 0, to days 14 and 35 in infected groups (P= 0.037, day 14) vs controls. The GFAP-positive cells in prenatally exposed brains showed 'hypertrophy' and more stellate morphology. These results implicate a significant role of prenatal human influenza viral infection on subsequent gliosis, which persists throughout brain development in mice from birth to adolescence.

Original languageEnglish (US)
Pages (from-to)633-640
Number of pages8
JournalMolecular psychiatry
Volume7
Issue number6
DOIs
StatePublished - 2002

Bibliographical note

Funding Information:
Supported by the National Alliance for Research on schizophrenia and depression, NARSAD established investigator award (Phyllis and Perry Schwartz investigator award), by University of Minnesota Medical Foundation (SHF) and NIH contract NO1-A1-65291 (RWS). Some of the data were presented at the Biological Psychiatry meeting in Washington, DC held in May 1999 and the 5th Stanley Neurovirology Symposium held in November 1999 in Bethesda, Maryland. We appreciate the dedicated secretarial help by Ms Janet Holland.

Keywords

  • Autism
  • GFAP
  • Infection
  • Influenza
  • Mice
  • Prenatal
  • Schizophrenia

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