Melatonin ameliorates sleep-wake disturbances and autism-like behaviors in the Ctnnd2 knock out mouse model of autism spectrum disorder

Abstract

Abstract Autism spectrum disorder (ASD) is a prevalent neurodevelopmental disorder characterized by atypical patterns of social interaction and communication as well as restrictive and repetitive behaviors. Additionally, ASD often presents with sleep disturbances. Delta (δ) catenin protein 2 (CTNND2) encodes δ-catenin protein, a neuron-specific catenin implicated in many complex neuropsychiatric diseases. Our previous study had exhibited deletion of Ctnnd2 in mice lead to autism-like behaviors. However, to our knowledge, no studies have investigated the effects of Ctnnd2 deletion in sleep of mice. In this study, we investigated whether knockout (KO) of exon 2 of the Ctnnd2 gene could induce sleep-wake disorders in mice and identify the effects of oral melatonin (MT) supplementation on KO mice. Our results demonstrated that KO mice exhibited ASD-like behaviors and sleep-wake disorders and they were attenuated, in part, by MT supplementation. Moreover, we further proved the correlation between autism-like behaviors and sleep-wake disorders in KO mice. MT may improve ASD-like behaviors by attenuating sleep-wake dysfunction. Overall, our current study was the first to identify that knockdown of Ctnnd2 gene could induce sleep-wake disorders in mice and had a correlation between sleep and phenotypes of ASD in Ctnnd2 KO mice. Our findings suggest that treatment of sleep-wake disturbances benefits on Ctnnd2 gene-deletion caused autism-like behaviors.