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

Scientists studied mice missing a specific gene (Ctnnd2) that's linked to autism. These mice showed autism-like behaviors and sleep problems. When researchers gave the mice melatonin (a natural sleep hormone), both the autism behaviors and sleep issues improved somewhat. This suggests melatonin might help children with autism who have sleep troubles, especially those with changes in this particular gene.

This preclinical study investigated sleep and autism-like behaviors in mice lacking the Ctnnd2 gene, which encodes a neuron-specific protein implicated in neuropsychiatric conditions. Researchers found that Ctnnd2 knockout mice exhibited both autism-like behaviors and sleep-wake disturbances. Importantly, oral melatonin supplementation partially improved both the behavioral symptoms and sleep problems in these mice. This represents the first study to demonstrate that Ctnnd2 gene deletion can cause sleep disorders in addition to autism-like behaviors, and suggests melatonin may have therapeutic potential for addressing sleep disturbances associated with this genetic variant.

Findings suggest melatonin may benefit autistic individuals with sleep disturbances, particularly those with Ctnnd2 genetic variants. Results support investigating melatonin as intervention for both sleep and core autism symptoms. Further human studies needed to validate these preclinical findings before clinical application.

Animal model findings may not directly translate to humans. Sample size not reported, limiting assessment of statistical power. Degree of improvement with melatonin described as 'partial' without specific quantification. Single gene knockout model may not reflect complex human autism genetics.

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. In addition, patients with 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 demonstrated that the deletion of Ctnnd2 in mice led to autism-like behaviors.

However, to our knowledge, no study has investigated the effects of Ctnnd2 deletion on sleep in mice. In this study, we investigated whether the knockout (KO) of exon 2 of the Ctnnd2 gene could induce sleep-wake disorders in mice and identified the effects of oral melatonin (MT) supplementation on Ctnnd2 KO mice. Our results demonstrated that the Ctnnd2 KO mice exhibited ASD-like behaviors and sleep-wake disorders that were partially attenuated by MT supplementation. Overall, our current study is the first to identify that knockdown of Ctnnd2 gene could induce sleep-wake disorders in mice and suggests that treatment of sleep-wake disturbances by MT may benefit to autism-like behaviors causing by Ctnnd2 gene deletion.