Maternal Stress Causes Behavioral Changes in C57BL/6J Mice

Background:   The etiology for most cases of autism spectrum disorder (ASD) is unknown at this time. There is strong evidence for the genetic role in ASD but environmental factors also have a modifying role.  One potential environmental factor is maternal stress during pregnancy. Stress during prenatal development increases the vulnerability of affective disorders including schizophrenia and ASD.  Prenatal stress has been shown to lead to postnatal behaviors that resemble the defining symptoms of ASD as well as other behaviors that occur frequently in ASD (Kinney et al., 2008).

Objectives: The objective of these experiments was to determine if restraint stress during pregnancy results in autistic-like behavioral alterations in the offspring. A commonly used inbred mouse strain, C57BL/6J was used because these mice to not typically have behaviors resembling the ASD phenotype.

Methods: Timed pregnant C57BL/6J mice were subject to restraint stress three times a day for 30 minutes, at least 2 hours apart for 9 days starting on GD11. The control pregnant mice were left undisturbed during gestation. Both male and female offspring from both stressed and control dams were behaviorally phenotyped as adults.  One female and male per litter were used in up to four tests, each test at least 2 days apart. The tests included the social approach test, elevated plus maze, light <--> dark box, marble burying, rotarod, open field and cued and contextual fear conditioning.

Results:   In general there were few differences between the male and female offspring. There were no significant effects of maternal stress in the offspring on tests of anxiety such as the elevated plus maze and light <--> dark box, obsessive-compulsive like behavior in the marble burying and spontaneous grooming tests,  motor ability and learning on the accelerating rotarod, or learning and memory assessed by the cued and contextual fear conditioning test. However, there were differences in social behavior and acute exploratory activity between the stressed and control mice. The offspring from the stressed dams were less social, spending less time sniffing the stranger mouse in the social approach test compared to the novel object. The stressed mice were also less active at the beginning of the open field exploration test, as shown by travelling a significantly smaller distance, having a reduced speed and spending more time immobile than the control mice.

Conclusions:   Prenatal restraint stress affected the behavior of these mice in ways that resemble one of the defining symptoms of ASD, decreased social behavior. Future testing with other inbred strains, including ones that are already considered mouse models of ASD will hopefully shed light on the contribution of prenatal stress to the etiology of ASD. This will provide information on a potentially preventable environmental factor associated with ASD.