Objective: To establish a maternal influenza infection model in pregnant mice and assess behavioral and pharmacological changes in adult offspring, including deficits in prepulse inhibition, exploratory behavior, and social interaction
Materials & Equipment Checklist
8 items1 from ConductScience
Gather these items before starting the experiment. Check off items as you prepare.
Equipment3
Not specified • Not mentioned • Not mentioned • Not mentioned
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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 respiratory infection with influenza virus
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; offspring are tested as adults
View evidence from paper
“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”
2
Prepulse inhibition testing
Adult offspring are tested for deficits in prepulse inhibition in the acoustic startle response
“these offspring display deficits in prepulse inhibition (PPI) in the acoustic startle response. Compared with control mice”
3
Acute drug administration testing
Adult offspring receive acute administration of antipsychotic drugs (clozapine, chlorpromazine) and psychomimetic drug (ketamine) to assess pharmacological responses
Not specifiedNot specified
Note: Infected mice display striking responses compared to controls
View evidence from paper
“striking responses to the acute administration of antipsychotic (clozapine and chlorpromazine) and psychomimetic (ketamine) drugs”
4
Open-field testing
Adult offspring are tested in open-field apparatus to measure exploratory behavior
Not specifiedNot specified
Note: Infected mice show deficient exploratory behavior compared to controls
View evidence from paper
“deficient in exploratory behavior in both open-field and novel-object tests”
5
Novel-object testing
Adult offspring are tested with novel objects to measure exploratory behavior
Not specifiedNot specified
Note: Infected mice show deficient exploratory behavior compared to controls
View evidence from paper
“deficient in exploratory behavior in both open-field and novel-object tests”
6
Social interaction testing
Adult offspring are assessed for social interaction deficits
Not specifiedNot specified
Note: Infected mice are deficient in social interaction
View evidence from paper
“they are deficient in social interaction”
7
Maternal poly(I:C) injection control
Pregnant mice receive maternal injection of synthetic double-stranded RNA polyinosinic-polycytidylic acid to test if immune response alone causes behavioral changes
Not specifiedNot specified
Note: This control tests whether maternal immune response, independent of viral infection, causes 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 offspring (age at testing not specified)
Sex
Not specified
Count
Not specified
Weight
Not specified
Pregnant dams infected during gestation; offspring tested as adults