0032 Identification Of A Muscle Function Protein In Brain Through A Proteomic Screen In Identification Of A Muscle Function Protein In Brain Through A Proteomic Screen In Sleep-deprived Mice. (12th April 2019)

• Record Type: Journal Article
• Authors: Brager, Allison J; Tummings, Ericka; Zhou, An; Ehlen, J Chris; Paul, Ketema
• Is Part Of: Sleep. Volume 42(2019)Supplement 1
• Page Start: A12
• Page End: A13
• Publication Date: 2019-04-12
• 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/zsz067.031
• Languages: English
• ISSNs: 0161-8105

Abstract

Abstract: Introduction: Recently, we identified that a clock protein in skeletal muscle has the ability to alter recovery responses to sleep deprivation, presenting evidence for a muscle-brain axis of sleep regulation (Ehlen et al. 2017). Here, we continue a search for mechanism of action through a proteomic screen in C57BL/6J mice (same background as Ehlen et al. 2017). Methods: Male mice (6 mo old), were subjected to 1 or 24 h of continuous sleep deprivation achieved on a motorized wheel beginning at lights-on. Mice subjected to sleep deprivation were then restrained (canonical tube method) or gently handled for 1 h (n=9 - 11 per group). Results: Through a proteomic screen of brain tissue (cortex) and plasma subjected to bioinformatics analyses, we found two key patterns of hits supporting the muscle-brain axis of sleep regulation. In both cases, the peak analyses for significance was set at > 60. First, there was a significant difference in PLMN (plasminogen) expression between mice sleep deprived for 1 h vs 24 h. Recent evidence has found sub-cellular localization of a plasminogen factor in the SCN circadian clock that is necessary and sufficient for photic phase re-setting (Hunley et al. 2015). Second, we found a significant hit for a muscle function protein (COL5a1) in only brain and not plasma of sleep-deprived mice that were restrained. COL5a1 is a genetic determinant of Ehlers-Paulos syndrome - chronic pain in joints and muscle (Pabalan et al. 2018). Chronic fatigue is a symptom of EDS (Hakim et al. 2017). Conclusion: To conclude, our proteomic screen has further narrowed down a putative mechanism of action for the ability of skeletal muscle to regulate sleep processes. Support (If Any): F32HL116077 to AB