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View Abstract
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.
Protocol Steps
1
Maternal viral infection
Pregnant mice (BALB/c and C57BL/6 strains) are infected via respiratory route with human influenza virus
not specifiednot specified
Note: Infection occurs during pregnancy to produce offspring with behavioral abnormalities
View evidence from paper
“respiratory infection of pregnant mice (both BALB/c and C57BL/6 strains) with the human influenza virus yields offspring”
2
Offspring maturation to adulthood
Offspring are allowed to develop to adulthood for behavioral testing
not specifiednot specified
Note: Behavioral testing occurs in adult offspring
View evidence from paper
“yields offspring that display highly abnormal behavioral responses as adults”
3
Social interaction testing
Adult offspring are tested for deficits in social interaction
not specifiednot specified
Note: Infected mice show deficiency in social interaction compared to control mice
View evidence from paper
“they are deficient in social interaction”
4
Open-field testing
Offspring are tested in open-field apparatus to measure exploratory behavior
not specifiednot specified
Note: Infected mice show deficiency in exploratory behavior
View evidence from paper
“deficient in exploratory behavior in both open-field and novel-object tests”
5
Novel-object testing
Offspring are tested with novel objects to measure exploratory behavior
not specifiednot specified
Note: Infected mice show deficiency in exploratory behavior
View evidence from paper
“deficient in exploratory behavior in both open-field and novel-object tests”
6
Prepulse inhibition (PPI) testing
Acoustic startle response is measured with prepulse inhibition paradigm
Note: Infected offspring display deficits in PPI similar to schizophrenia and autism
View evidence from paper
“display deficits in prepulse inhibition (PPI) in the acoustic startle response”
7
Acute antipsychotic drug administration
Clozapine and chlorpromazine are administered acutely to test pharmacological responses
not specifiednot specified
Note: Infected mice show striking responses to antipsychotic drugs
View evidence from paper
“striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine)”
8
Acute psychomimetic drug administration
Ketamine is administered acutely to test pharmacological responses
not specifiednot specified
Note: Infected mice show striking responses to psychomimetic drugs
View evidence from paper
“striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs”
9
Maternal immune response induction control
Pregnant mice are injected with synthetic double-stranded RNA (poly(I:C)) to induce maternal immune response without viral infection
not specifiednot specified
Note: This control demonstrates that maternal immune response alone can cause PPI deficits in offspring
View evidence from paper
“maternal injection of the synthetic double-stranded RNA polyinosinic-polycytidylic acid causes a PPI deficit in the offspring in the absence of virus”
Subjects / Specimens
Species
mouse
Strain
BALB/c and C57BL/6
Age
adult
Sex
not specified
Count
not specified
Weight
not specified
Offspring of pregnant mice infected with human influenza virus during gestation