Circadian regulation of sleep in a pre-clinical model of Dravet syndrome: dynamics of sleep stage and siesta re-entrainment

• Published in: Sleep (New York, N.Y.) Vol. 42; no. 12; p. 1
• Main Authors: Sanchez, Raymond E A, Bussi, Ivana L, Ben-Hamo, Miriam, Caldart, Carlos S, Catterall, William A, de la Iglesia, Horacio O
• Format: Journal Article
• Language: English
• Published: US Oxford University Press 01-12-2019
• Subjects: Animals; Basic Science of Sleep and Circadian Rhythms; Circadian Clocks - physiology; Circadian rhythm; Circadian Rhythm - physiology; Electrocorticography - methods; Epilepsies, Myoclonic - genetics; Epilepsies, Myoclonic - physiopathology; Epilepsy; Female; Jet Lag Syndrome - genetics; Jet Lag Syndrome - physiopathology; Laws, regulations and rules; Male; Medical research; Mice; Mice, Inbred C57BL; Mice, Transgenic; NAV1.1 Voltage-Gated Sodium Channel - genetics; Sleep; Sleep disorders; Sleep Stages - physiology; Sleep Wake Disorders - genetics; Sleep Wake Disorders - physiopathology; epilepsy; siesta; Dravet syndrome; circadian rhythm; sleep timing; jet lag; sleep re-entrainment; circadian sleep regulation
• ISSN: 0161-8105; 1550-9109
• DOI: 10.1093/sleep/zsz173

Abstract
Study Objectives
Sleep disturbances are common co-morbidities of epileptic disorders. Dravet syndrome (DS) is an intractable epilepsy accompanied by disturbed sleep. While there is evidence that daily sleep timing is disrupted in DS, the difficulty of chronically recording polysomnographic sleep from patients has left our understanding of the effect of DS on circadian sleep regulation incomplete. We aim to characterize circadian sleep regulation in a mouse model of DS.
Methods
Here we exploit long-term electrocorticographic recordings of sleep in a mouse model of DS in which one copy of the Scn1a gene is deleted. This model both genocopies and phenocopies the disease in humans. We test the hypothesis that the deletion of Scn1a in DS mice is associated with impaired circadian regulation of sleep.
Results
We find that DS mice show impairments in circadian sleep regulation, including a fragmented rhythm of non-rapid eye movement (NREM) sleep and an elongated circadian period of sleep. Next, we characterize re-entrainment of sleep stages and siesta following jet lag in the mouse. Strikingly, we find that re-entrainment of sleep following jet lag is normal in DS mice, in contrast to previous demonstrations of slowed re-entrainment of wheel-running activity. Finally, we report that DS mice are more likely to have an absent or altered daily “siesta”.
Conclusions
Our findings support the hypothesis that the circadian regulation of sleep is altered in DS and highlight the value of long-term chronic polysomnographic recording in studying the role of the circadian clock on sleep/wake cycles in pre-clinical models of disease.