001 Exploring the Orexin-tTA/TetO-DTA Mouse as a Model for Pediatric Narcolepsy. (3rd May 2021)

• Record Type: Journal Article
• Authors: Joyal, Adam; Yamanaka, Akihiro; Scammell, Thomas; Coffey, Alissa
• Is Part Of: Sleep. Volume 44(2021)Supplement 2
• Page Start: A1
• Page End: A1
• Publication Date: 2021-05-03
• Subjects: Sleep -- Physiological aspects -- Periodicals; Sleep disorders -- Periodicals; Sommeil -- Aspect physiologique -- Périodiques; Sommeil, Troubles du -- Périodiques; Sleep disorders; Sleep -- Physiological aspects; Sleep -- physiological aspects; Sleep Wake Disorders; Psychophysiology; Electronic journals; Periodicals; 616.8498
• DOI: 10.1093/sleep/zsab072.000
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Introduction: Narcolepsy is a sleep disorder caused by selective death of the orexin neurons that often begins in childhood. Orexin neuron loss disinhibits REM sleep during the active period and produces cataplexy, an abnormal behavioral state between REM sleep and wakefulness. Cataplexy is often more severe when narcolepsy develops in children compared to adults, but the mechanisms underlying this difference remain unknown. Methods: We used orexin-tTA/TetO-DTA mice to model narcolepsy at different ages. When doxycycline is removed from the diet, the orexin neurons of these mice express diphtheria toxin A and die within 2–3 weeks. We removed doxycycline at 4 weeks (young-onset) or 14 weeks (adult-onset) of age in male and female mice. We implanted EEG and EMG electrodes for sleep recordings one week later and then recorded EEG/EMG/video for 24h at 3 and 13 weeks after removal of doxycycline. Age-matched controls had access to doxycycline diet for the entire experiment. Results: Three weeks after doxycycline removal, both young-onset and adult-onset mice developed cataplexy and the sleep-wake fragmentation characteristic of narcolepsy. Age of orexin cell loss did not significantly affect cataplexy severity, however, female mice had more cataplexy than male mice overall. Both young- and adult-onset mice showed a 99% loss of orexin neurons at 3 weeks. Conclusion: Considered together, our results suggest that the orexin-tTA/TetO-DTA mouse model of narcolepsy does not capture the severe cataplexy that is often seen in the human pediatric population. Support (if any):