The Transgenerational Effects of Prenatal Maternal Voluntary Wheel Running on Autistic Characteristics in BTBR T+ Itp3 Tf/J Mice

Background: Autism spectrum disorder (ASD) is a group of neurodevelopmental disorders that are characterized by deficits in social communication and restricted, repetitive patterns of behavior, interests, or activities. Prenatal exercise is thought to be beneficial for fetal brain development and was examined in the BTBR T⁺ Itpr3 ^tf/J (BTBR) inbred strain of mice that is often compared to the more typical C57BL/6J (B6) mice. The BTBR mice exhibit reduced sociability and high levels of repetitive behaviors compared to the B6 mice. The transgenerational effects of prenatal paternal voluntary exercise have been examined briefly in the B6 mice, but prenatal maternal voluntary exercise has not been studied in either strain.

Objectives: To determine if maternal voluntary exercise perinatally leads to lessened autistic-like behaviors in the BTBR offspring.

Methods: In this study, female B6 and BTBR females were given access to running wheels in the home cage for an 8-week period, beginning 2 weeks prior to breeding and continuing until the pups were weaned. The offspring were allowed to age with minimal intervention and were examined as adults. Sociability, anxiety, repetitive behaviors, and learning and memory were tested and compared to the offspring from non-wheel exposed controls from both strains, to determine if prenatal maternal exercise altered these behaviors.

Results: Prenatal exercise only affected a few behaviors in the offspring, and those effects were often the opposite of what was expected. For example, wheel running had only a mild effect on the autistic-like behaviors found in the BTBR mice. Social behavior was unchanged in the BTBR mice following prenatal exercise exposure. Repetitive behaviors were mildly affected, as the male BTBR mice exposed to prenatal wheel running spent more time grooming than any of the other mice in the open field, and all of the BTBR offspring from the wheel running dams were impaired in reversal learning in the water T-maze. However, despite this influence on self-grooming and reversal learning, voluntary wheel running did not affect repetitive digging in the marble burying test. BTBR mice exposed to prenatal maternal voluntary wheel running also showed increased anxiety associated behaviors.

Conclusions: Maternal voluntary exercise appears to mildly increase the development of repetitive behaviors but not social behaviors in the BTBR mice and had a mild effect of increasing anxiety-like behaviors. Thus, these results suggest that maternal voluntary wheel running does not lessen autistic-like behaviors in the BTBR mice.