IN UTERO EXPOSURE TO INFLUENZA
A/WSN/33 VIRUS; TRANSPLACENTAL PASSAGE , PERSISTENCE AND INFLUENCE ON FETAL
BRAIN GENE EXPRESSION
Frederik Aronsson, Charlotta Lannebo,
Martin Paucar, Johan Brask, Krister Kristensson and Håkan Karlsson
Department of Neuroscience,
Karolinska Institute, Stockholm, Sweden
Epidemiological studies have identified
a number of environmental factors associated with the development of
schizophrenia. One possible environmental factor may be infections during
early life. It has been reported that individuals exposed to the 1957 type
A2 influenza epidemic during the 2nd trimester of gestation were at greater risk
of being diagnosed with schizophrenia than unexposed control subjects.
There are no existing animal models of schizophrenia but we can, however, use
animals to test some of the hypotheses put forward by psychiatric
researchers. By studying the entire lifespan of an animal we can
investigate neurodevelopmental and lifelong effects of environmental insults,
quite difficult to perform in humans.
Pregnant C57B1/6 mice were inoculated
intranasally, with the mouse adapted neurotropic influenza A/WSN/33 virus at day
14 of gestation. On day 17 of gestation total RNA was extracted from fetal
brains, lungs and corresponding placentas. Viral RNA was detected in
placentas (8/26) and in fetal brains (4/26) and lungs (7/26) indicating
transplacental passage of the virus. Gene expression profiling was performed on
RNA pools from brains of fetuses exposed and unexposed to virus,
respectively. Forty RNA species were considered differentially expressed
in these pools. The expression levels of 10 of these genes are currently
being verified in the individual brains by means of semi-quantitative PCR.