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bioRxiv · 10.1101/2025.10.09.676449

Hyperactivity is linked to elevated cortisol levels: comprehensive behavioral analysis in the prenatal valproic acid-induced marmoset model of autism

Nakamura, M.·Nakamura, T.·Nakagami, A.·Nakagaki, K.·Kawai, N.·Ichinohe, N.
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Abstract

Hyperactivity is frequently observed in individuals with autism spectrum disorder (ASD) and significantly affects various aspects of life. This underscores the critical need for effective intervention methods tailored to the needs of individuals with ASD. Non-human primate models offer a promising avenue for elucidating the intricate interplay between ASD characteristics and developing individualized therapeutic strategies. This study examined the activity levels and behavioral dynamics in a prenatal valproic acid-induced (VPA) common marmoset model of ASD using ultraminiature data loggers, employing a more detailed approach to behavioral pattern analysis than is traditionally utilized. Although the overall activity levels showed no significant differences, the VPA group exhibited increased activity during specific hours, which is consistent with human ASD studies. Sample Entropy, a statistical measure used to quantify the regularity and unpredictability of time-series data, was higher during daytime in the VPA group, indicating reduced regularity in activity patterns akin to impulsive behavior in ASD. Subtle patterns that were not discernible through simple group comparisons were identified, highlighting the potential of this method as a valuable tool for the behavioral analysis of human ASD. Associations between erratic activity patterns, brief resting intervals, and elevated cortisol levels were observed, all of which correspond to stress phenotypes in individuals with ASD. The findings revealed variations in activity among the adult VPA groups, potentially linked to stress responses. Additionally, VPA juvenile marmosets showed increased locomotor activity in the social interaction test, complementing the adult behavioral findings and suggesting age-dependent manifestations of hyperactivity in this model. This non-human primate model effectively replicates real-world scenarios encountered by individuals with ASD exhibiting hyperactivity, thus holding significant implications for the advancement of personalized therapeutic strategies.

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Nakamura, M., Nakamura, T., Nakagami, A., Nakagaki, K., Kawai, N., Ichinohe, N.. 2025-10-10. Hyperactivity is linked to elevated cortisol levels: comprehensive behavioral analysis in the prenatal valproic acid-induced marmoset model of autism. https://doi.org/10.1101/2025.10.09.676449

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