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Gender-dependent effects of maternal immune activation on the behavior of mouse offspring.

Xuan IC, Hampson DR - PLoS ONE (2014)

Bottom Line: Autism-associated behaviors were examined in the adult offspring of the treated dams.We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity.Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.

ABSTRACT
Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the "maternal immune activation" model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.

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Related in: MedlinePlus

Timeline for behavioral testing.The age of the mice in weeks is indicated.
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pone-0104433-g001: Timeline for behavioral testing.The age of the mice in weeks is indicated.

Mentions: To avoid potential complications from analyzing mice during the period when the brain is rapidly maturing, behavioral testing began in late adolescent mice at 6 weeks of age (Fig. 1). This corresponds to an age just prior to brain maturation in the mouse at 7–8 weeks postnatal. To reduce the effects of repeated measures, behavioral analyses were conducted one week apart. Video recording of grooming was conducted during the habituation period of social testing as well as during the social preference test.


Gender-dependent effects of maternal immune activation on the behavior of mouse offspring.

Xuan IC, Hampson DR - PLoS ONE (2014)

Timeline for behavioral testing.The age of the mice in weeks is indicated.
© Copyright Policy
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC4128679&req=5

pone-0104433-g001: Timeline for behavioral testing.The age of the mice in weeks is indicated.
Mentions: To avoid potential complications from analyzing mice during the period when the brain is rapidly maturing, behavioral testing began in late adolescent mice at 6 weeks of age (Fig. 1). This corresponds to an age just prior to brain maturation in the mouse at 7–8 weeks postnatal. To reduce the effects of repeated measures, behavioral analyses were conducted one week apart. Video recording of grooming was conducted during the habituation period of social testing as well as during the social preference test.

Bottom Line: Autism-associated behaviors were examined in the adult offspring of the treated dams.We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity.Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.

View Article: PubMed Central - PubMed

Affiliation: Department of Pharmaceutical Sciences, Leslie Dan Faculty of Pharmacy, University of Toronto, Toronto, Canada.

ABSTRACT
Autism spectrum disorders are neurodevelopmental disorders characterized by two core symptoms; impaired social interactions and communication, and ritualistic or repetitive behaviors. Both epidemiological and biochemical evidence suggests that a subpopulation of autistics may be linked to immune perturbations that occurred during fetal development. These findings have given rise to an animal model, called the "maternal immune activation" model, whereby the offspring from female rodents who were subjected to an immune stimulus during early or mid-pregnancy are studied. Here, C57BL/6 mouse dams were treated mid-gestation with saline, lipopolysaccharide (LPS) to mimic a bacterial infection, or polyinosinic:polycytidylic acid (Poly IC) to mimic a viral infection. Autism-associated behaviors were examined in the adult offspring of the treated dams. Behavioral tests were conducted to assess motor activity, exploration in a novel environment, sociability, and repetitive behaviors, and data analyses were carried independently on male and female mice. We observed a main treatment effect whereby male offspring from Poly IC-treated dams showed reduced motor activity. In the marble burying test of repetitive behavior, male offspring but not female offspring from both LPS and Poly IC-treated mothers showed increased marble burying. Our findings indicate that offspring from mothers subjected to immune stimulation during gestation show a gender-specific increase in stereotyped repetitive behavior.

Show MeSH
Related in: MedlinePlus