Early exposure to a methyl donor supplemented diet and the development of repetitive motor behavior in a mouse model.

Motor behaviors that are repetitive and exhibit little variability in form are common in neurodevelopmental disorders (e.g., autism spectrum disorder). C58 mice exhibit persistent, high levels of repetitive motor behavior when reared in restricted, but not enriched, environments implicating epigenetic mechanisms (e.g., DNA methylation). We sought to determine if alteration of DNA methylation played a role in the development of repetitive behavior in C58 mice. Thus, we tested the hypothesis that early exposure (in utero and preweaning) to a methyl donor supplemented diet would alter the developmental trajectory of repetitive behavior. Such dietary exposure resulted in significant attenuation of repetitive motor behavior development, persisting through early adulthood. This was despite mice being housed in standard cages and maintained on a standard diet, postweaning. Early exposure to methyl donor supplementation not only affected the frequency of repetitive behavior but also its temporal structure, resulting in more variable patterns of repetitive behavior. Early exposure to the diet was also shown to induce long-lasting increases in DNA methylation in brain tissue of female mice. The role for alterations in DNA methylation in this model may be one mechanism accounting for the robust effects of the environment on the development of repetitive behavior.

Repetitive motor behavior: further characterization of development and temporal dynamics.

Repetitive behaviors are diagnostic for autism spectrum disorders, common in related neurodevelopmental disorders, and normative in typical development. In order to identify factors that mediate repetitive behavior development, it is necessary to characterize the expression of these behaviors from an early age. Extending previous findings, we characterized further the ontogeny of stereotyped motor behavior both in terms of frequency and temporal organization in deer mice. A three group trajectory model provided a good fit to the frequencies of stereotyped behavior across eight developmental time points. Group based trajectory analysis using a measure of temporal organization of stereotyped behavior also resulted in a three group solution. Additionally, as the frequency of stereotyped behavior increased with age, the temporal distribution of stereotyped responses became increasingly regular or organized indicating a strong association between these measures. Classification tree and principal components analysis showed that accurate classification of trajectory group could be done with fewer observations. This ability to identify trajectory group membership earlier in development allows for examination of a wide range of variables, both experiential and biological, to determine their impact on altering the expected trajectory of repetitive behavior across development. Such studies would have important implications for treatment efforts in neurodevelopmental disorders such as autism.