Dim light at night disrupts the sleep-wake cycle and exacerbates abnormal EEG activity in Cntnap2 knockout mice: implications for autism spectrum disorders.

Abstract

BACKGROUND: Epilepsy is a common comorbidity in individuals with autism spectrum disorders (ASDs). Many patients with epilepsy as well as ASD experience disruptions in their sleep-wake cycle and daily fluctuations in symptom severity. Chronic exposure to light at nighttime can disrupt sleep and circadian rhythms. Contactin associated protein-like 2 knockout (Cntnap2 KO) mice, a model of ASD and epilepsy, exhibit sleep and circadian disturbances and abnormal events in the electroencephalogram (EEG). Here, we investigated how chronic dim light at night (DLaN) exposure affects sleep architecture, EEG power spectra, and abnormal EEG events in Cntnap2 KO and wildtype (WT) mice. METHODS: Male and female Cntnap2 KO and WT mice were exposed to DLaN (5 lx) for 6 weeks. EEG recordings were collected and analyzed to assess sleep architecture, spectral power, and abnormal EEG events. A two-way repeated-measures analysis of variance (ANOVA) was used to evaluate the effects of DLaN across time and EEG frequencies, followed by Bonferroni-corrected post hoc tests where appropriate. RESULTS: DLaN exposure delayed wake onset and disrupted 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, consistent with increased sleep pressure. Notably, DLaN markedly elevated the frequency of abnormal hypersynchronized EEG events in Cntnap2 KO mice and even induced such events in WT mice. Spectral analysis of abnormal EEG events revealed elevated theta power, suggesting hippocampal involvement. CONCLUSIONS: Chronic DLaN exposure disrupts sleep architecture in a sex-dependent fashion and increases the occurrence of abnormal EEG events in Cntnap2 KO mice. These findings highlight the potential risks of nighttime light exposure for individuals with ASD and epilepsy, underscoring the importance of managing light environments to improve sleep quality and neurological health.