Limits...
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.

Show MeSH

Related in: MedlinePlus

The effects of maternal immune activation on social behavior in the three-chamber social interaction test.(A) diagrammatic depiction of the experimental set-up for the social interaction test. (B) Male and female saline-treated mice showed the expected preference for the social zone (**p<0.01; ***p<0.001; ****p<0.0001). However, compared to saline-treated controls, female LPS and Poly IC offspring showed no significant preference for the social zone over the non-social zone. A loss of the normal social interaction behavior was also observed in male Poly IC mice, but not in male LPS mice compared to control mice. Each column represents mean ± S.E.M.
© Copyright Policy
Related In: Results  -  Collection

License
getmorefigures.php?uid=PMC4128679&req=5

pone-0104433-g003: The effects of maternal immune activation on social behavior in the three-chamber social interaction test.(A) diagrammatic depiction of the experimental set-up for the social interaction test. (B) Male and female saline-treated mice showed the expected preference for the social zone (**p<0.01; ***p<0.001; ****p<0.0001). However, compared to saline-treated controls, female LPS and Poly IC offspring showed no significant preference for the social zone over the non-social zone. A loss of the normal social interaction behavior was also observed in male Poly IC mice, but not in male LPS mice compared to control mice. Each column represents mean ± S.E.M.

Mentions: Social impairment is one of the core symptoms of ASD and is often linked with deficits in communication. In rodents this behavior can be assessed using three-chamber testing paradigms [34]. The test is divided into two stages. In the social interaction test, sociability was measured by comparing the time the animal spent in the zone with a novel mouse (the social zone) versus a novel object (non-social zone; Fig. 3A). In the second stage, termed the social preference test, sociability was measured by comparing the time the animal spent in the zone with a familiar mouse (the familiar zone) versus a new non-familiar mouse (the non-familiar zone, Figure S3A). In both tests, normal social behavior entailed significant preference for the social and non-familiar zones over the non-social and familiar zones, respectively.


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

Xuan IC, Hampson DR - PLoS ONE (2014)

The effects of maternal immune activation on social behavior in the three-chamber social interaction test.(A) diagrammatic depiction of the experimental set-up for the social interaction test. (B) Male and female saline-treated mice showed the expected preference for the social zone (**p<0.01; ***p<0.001; ****p<0.0001). However, compared to saline-treated controls, female LPS and Poly IC offspring showed no significant preference for the social zone over the non-social zone. A loss of the normal social interaction behavior was also observed in male Poly IC mice, but not in male LPS mice compared to control mice. Each column represents mean ± S.E.M.
© Copyright Policy
Related In: Results  -  Collection

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

pone-0104433-g003: The effects of maternal immune activation on social behavior in the three-chamber social interaction test.(A) diagrammatic depiction of the experimental set-up for the social interaction test. (B) Male and female saline-treated mice showed the expected preference for the social zone (**p<0.01; ***p<0.001; ****p<0.0001). However, compared to saline-treated controls, female LPS and Poly IC offspring showed no significant preference for the social zone over the non-social zone. A loss of the normal social interaction behavior was also observed in male Poly IC mice, but not in male LPS mice compared to control mice. Each column represents mean ± S.E.M.
Mentions: Social impairment is one of the core symptoms of ASD and is often linked with deficits in communication. In rodents this behavior can be assessed using three-chamber testing paradigms [34]. The test is divided into two stages. In the social interaction test, sociability was measured by comparing the time the animal spent in the zone with a novel mouse (the social zone) versus a novel object (non-social zone; Fig. 3A). In the second stage, termed the social preference test, sociability was measured by comparing the time the animal spent in the zone with a familiar mouse (the familiar zone) versus a new non-familiar mouse (the non-familiar zone, Figure S3A). In both tests, normal social behavior entailed significant preference for the social and non-familiar zones over the non-social and familiar zones, respectively.

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