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

Apr 8, 2025bioRxiv : the preprint server for biology

Dim Light at Night Disturbs Sleep and Increases Seizures in Mice Lacking a Key Brain Protein Linked to Autism

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Abstract

Chronic dim light at night exposure significantly increases seizure-like events in contactin associated protein-like 2 knockout (KO) mice.

Sleep patterns are disrupted by chronic dim light at night, with females showing greater sensitivity than males.
Dim light exposure results in increased slow-wave activity, suggesting heightened sleep pressure in both knockout and wildtype mice.
The frequency of seizure-like events is dramatically increased in KO mice and also rises in wildtype mice following dim light exposure.
Analysis indicates elevated theta power during seizure-like events, implicating hippocampal involvement.
Findings highlight potential risks associated with nighttime light exposure for individuals with autism spectrum disorder and epilepsy.

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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 (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 inKO and wildtype (WT) mice. Using electroencephalography (EEG) recordings, male and femaleKO 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 inKO 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. Cntnap2Cntnap2Cntnap2Cntnap2

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

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