Maternal Influenza Infection Causes Marked Behavioral and Pharmacological Changes in the Offspring

Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly a...

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Bibliographic Details
Published in:The Journal of neuroscience 2003-01, Vol.23 (1), p.297-302
Main Authors: Shi, Limin, Fatemi, S. Hossein, Sidwell, Robert W, Patterson, Paul H
Format: Article
Language:English
Subjects:
Acoustic Stimulation
Animals
Animals, Newborn
Antipsychotic Agents - pharmacology
Antiviral Agents - pharmacology
Anxiety
Behavior, Animal
Chlorpromazine - pharmacology
Clozapine - pharmacology
Exploratory Behavior
Female
Immunity
Ketamine - pharmacology
Maternal-Fetal Relations
Mice
Mice, Inbred BALB C
Mice, Inbred C57BL
Motor Activity
Orthomyxoviridae Infections - psychology
Poly I-C - pharmacology
Pregnancy
Social Behavior
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Summary:Maternal viral infection is known to increase the risk for schizophrenia and autism in the offspring. Using this observation in an animal model, we find that respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring that display highly abnormal behavioral responses as adults. As in schizophrenia and autism, these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice, the infected mice also display striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs. Moreover, these mice are deficient in exploratory behavior in both open-field and novel-object tests, and they are deficient in social interaction. At least some of these behavioral changes likely are attributable to the maternal immune response itself. That is, maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus. Therefore, maternal viral infection has a profound effect on the behavior of adult offspring, probably via an effect of the maternal immune response on the fetus.
ISSN:0270-6474
1529-2401
DOI:10.1523/jneurosci.23-01-00297.2003