Prenatal viral infection causes alterations in nNOS expression in developing mouse brains

Neuroreport. 2000 May 15;11(7):1493-6.

Abstract

Epidemiological evidence points to prenatal viral infection being responsible for some forms of schizophrenia and autism. We hypothesized that prenatal human influenza viral infection in day 9 pregnant mice may cause changes in the levels of neuronal nitric oxide synthase (nNOS), an important molecule involved in synaptogenesis and excitotoxicity, in neonatal brains. Brains from 35- and 56-day-old mice were prepared for SDS-gel electrophoresis and Western blotting using polyclonal anti nNOS antibody. Quantification of nNOS showed time and region-dependent changes in the levels of nNOS protein. Mean rostral brain area value from prenatally infected animals showed a significant (p=0.067) increase of 147% in nNOS levels at 35 days postnatally, with an eventual 29% decrease on day 56. Middle and caudal brain areas showed reductions in nNOS in experimental mice at 35 and 56 days, with a significant 27% decrease in nNOS in the middle segment of day 56 brains (p=0.016). Significant interactions were found between group membership and brain area (Wilks lambda=0.440, F(2.9)=5.72, p=0.025); there was also a significant interaction between brain area, group and age (Wilks lambda=0.437, F(2.9)=5.79, p=0.024). These results provide further support for the notion that prenatal viral infection affects brain development adversely via the pathological involvement of nNOS expression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Autistic Disorder / virology
  • Brain / embryology*
  • Brain / enzymology*
  • Encephalitis, Viral / enzymology*
  • Female
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nitric Oxide Synthase / analysis
  • Nitric Oxide Synthase / metabolism*
  • Nitric Oxide Synthase Type I
  • Orthomyxoviridae Infections / enzymology*
  • Pregnancy
  • Prenatal Exposure Delayed Effects
  • Schizophrenia / virology
  • Specific Pathogen-Free Organisms

Substances

  • Nitric Oxide Synthase
  • Nitric Oxide Synthase Type I
  • Nos1 protein, mouse