4.7 Article

Melatonin treatment of repetitive behavioral deficits in the Cntnap2 mouse model of autism spectrum disorder

Journal

NEUROBIOLOGY OF DISEASE
Volume 145, Issue -, Pages -

Publisher

ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.nbd.2020.105064

Keywords

Autism spectrum disorder; Circadian; Cntnap2; Light pollution; Melatonin; Mice

Categories

Funding

  1. UCLA Center for Autism Research and Treatment (CART)
  2. UCLA Clinical and Translational Science Institute (NIH) [UL1TR001881]
  3. National Institute of Child Health Development [5U54HD087101]

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Nighttime light pollution is linked to metabolic and cognitive dysfunction. Many patients with autism spectrum disorders (ASD) show disturbances in their sleep/wake cycle, and may be particularly vulnerable to the impact of circadian disruptors. In this study, we examined the impact of exposure to dim light at night (DLaN, 5 lx) in a model of ASD: the contactin associated protein-like 2 knock out (Cntnap2 KO) mice. DLaN was sufficient to disrupt locomotor activity rhythms, exacerbate the excessive grooming and diminish the social preference in Cntnap2 mutant mice. On a molecular level, DLaN altered the phase and amplitude of PER2:LUC rhythms in a tissue-specific manner in vitro. Daily treatment with melatonin reduced the excessive grooming of the mutant mice to wild-type levels and improved activity rhythms. Our findings suggest that common circadian disruptors such as light at night should be considered in the management of ASD.

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