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

Neurobiol Dis. 2020 Nov:145:105064. doi: 10.1016/j.nbd.2020.105064. Epub 2020 Sep 2.

Abstract

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.

Keywords: Autism spectrum disorder; Circadian; Cntnap2; Light pollution; Melatonin; Mice.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Autism Spectrum Disorder* / genetics
  • Behavior, Animal / drug effects
  • Central Nervous System Depressants / pharmacology*
  • Circadian Rhythm / drug effects*
  • Disease Models, Animal
  • Lighting / adverse effects*
  • Melatonin / pharmacology*
  • Membrane Proteins / deficiency
  • Membrane Proteins / genetics
  • Mice
  • Mice, Knockout
  • Nerve Tissue Proteins / deficiency
  • Nerve Tissue Proteins / genetics

Substances

  • CNTNAP2 protein, mouse
  • Central Nervous System Depressants
  • Membrane Proteins
  • Nerve Tissue Proteins
  • Melatonin