Prenatal viral infection causes alterations in nNOS... : NeuroReport (original) (raw)
DEVELOPMENTAL NEUROSCIENCE
Prenatal viral infection causes alterations in nNOS expression in developing mouse brains
Fatemi, S Hossein; Cuadra, Adolfo E.; El-Fakahany, Esam E.; Sidwell, Robert W.; Thuras, Paul
1 Department of Psychiatry, Division of Neuroscience Research, University of Minnesota Medical School, Box 392 Mayo bldg, 420 Delaware St. SE Minneapolis, MN 55455, USA
2 Institute for antiviral research, Utah State University, 5600 University Blvd, Logan UT, 84322-5600, USA
3 Corresponding Author: S. Hossein Fatemi
Acknowledgements: We are grateful to NARSAD, the Minnesota Medical Foundation and the department of psychiatry Faculty seed grant for provision of funds to carry out this project. S.H.F. is an established Phyllis and Perry Schwartz NARSAD investigator. R.S. was supported by NIAID contract No. 1-AI65291. E.E.-F. was supported by NIH grant RO1 NS25743. We are grateful to Dr Paula Clayton for her enthusiastic support throughout this project.
Received 1 February 2000; accepted 1 March 2000
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.
© 2000 Wolters Kluwer Health | Lippincott Williams & Wilkins