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Early exposure to a methyl donor supplemented diet and the development of repetitive motor behavior in a mouse model
Amber M Muehlmann1, Nikolay Bliznyuk2, Isaac Duerr2
1Department of Psychiatry, University of Florida, Gainesville, FL, USA.
Abstract:
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.
Insights
Early exposure to a methyl donor diet reduced repetitive motor behaviors in mice, suggesting a role for DNA methylation in neurodevelopmental disorders. This intervention promoted more variable behavior patterns.
Area of Science:
- Neuroscience
- Developmental Biology
- Epigenetics
Background:
- Repetitive motor behaviors are common in neurodevelopmental disorders like autism spectrum disorder.
- C58 mice show high levels of repetitive behavior in restricted environments, suggesting epigenetic involvement.
- DNA methylation is a key epigenetic mechanism potentially influencing these behaviors.
Purpose of the Study:
- To investigate if early exposure to a methyl donor supplemented diet alters the development of repetitive motor behavior in C58 mice.
- To determine the role of DNA methylation in mediating environmental effects on repetitive behavior.
Main Methods:
- Administered a methyl donor supplemented diet to C58 mice during gestation and preweaning periods.
- Assessed repetitive motor behavior frequency and temporal structure from early development through adulthood.
- Measured DNA methylation levels in brain tissue, particularly in female mice.
Main Results:
- Early methyl donor diet exposure significantly attenuated the development of repetitive motor behaviors.
- The reduction in repetitive behaviors persisted into early adulthood, even on a standard diet.
- Dietary intervention altered the temporal structure of repetitive behaviors, increasing variability.
- Long-lasting increases in DNA methylation were observed in the brain tissue of female mice exposed to the diet.
Conclusions:
- Early life nutritional interventions, specifically methyl donor supplementation, can modify the trajectory of repetitive motor behaviors.
- DNA methylation alterations in early development may be a crucial mechanism linking environmental factors to behavioral outcomes in neurodevelopmental contexts.
- This study provides evidence for the role of epigenetic modifications in the development of repetitive behaviors, offering potential targets for intervention.
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