IN UTERO EXPOSURE TO INFLUENZA A

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.