Dim Light at Night Disrupts the Sleep-Wake Cycle and Exacerbates Seizure Activity in Cntnap2 Knockout Mice: Implications for Autism Spectrum Disorders

Abstract

Epilepsy is one of the most common comorbidities in individuals with autism spectrum disorders (ASDs). Many patients with epilepsy as well as ASD experience disruptions in their sleep-wake cycle and exhibit daily rhythms in expression of symptoms. Chronic exposure to light at nighttime can disrupt sleep and circadian rhythms. Contactin associated protein-like 2 knockout (Cntnap2 KO) mice, a model for autism spectrum disorder (ASD) and epilepsy, exhibit sleep and circadian disturbances and seizure-like events. This study examines how chronic dim light at night (DLaN) exposure affects sleep architecture, EEG power spectra, and seizure activity in Cntnap2 KO and wildtype (WT) mice. Using electroencephalography (EEG) recordings, male and female Cntnap2 KO and WT mice were exposed to DLaN (5 lux) for 2 or 6 weeks. EEG recordings were analyzed to assess sleep architecture, power spectrum, and seizure-like events. DLaN exposure delays the wake onset and disrupts sleep patterns in a sex-dependent manner, with females being more affected. DLaN significantly increased slow-wave activity (SWA, 0.5-4 Hz) in both WT and KO mice, indicating increased sleep pressure. Finally, we found that DLaN dramatically increased the frequency of seizure-like events in the Cntnap2 KO mice and even increased the occurrence rate in the WT mice. Spectral analysis of seizure-like events revealed increased theta power, suggesting the involvement of hippocampus. Chronic DLaN exposure disrupts sleep and increases seizure-like events in Cntnap2 KO mice, with sex-specific differences. These findings emphasize the potential risks of nighttime light exposure for individuals with ASD and epilepsy, reinforcing the need to manage light exposure to improve sleep quality and reduce seizure risk.