Yumi Okoshi1, Naoyuki Tanuma2, Rie Miyata3, Masaharu Hayashi4. 1. Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan; Department of Pediatrics, Hokkaido University Graduate School of Medicine, Hokkaido, Japan; Department of Pediatrics, Tokyo Metropolitan Fuchu Medical Center for the Disabled, Tokyo, Japan. 2. Department of Pediatrics, Tokyo Metropolitan Fuchu Medical Center for the Disabled, Tokyo, Japan. 3. Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. 4. Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. Electronic address: hayashi-ms@igakuken.or.jp.
Abstract
BACKGROUND: Cockayne syndrome (CS) is a genetic disorder caused by deficient nucleotide excision repair. Patients with CS exhibit progeroid features, developmental delay, and various neurological disorders; they are also known to suffer from sleep problems, which have never been investigated in detail. OBJECTIVE: The aim of this study is to investigate the pathogenesis of sleep disorders in patients with CS. METHODS: We performed a questionnaire survey of the families of patients with CS, enzyme-linked immunosorbent analyses of the melatonin metabolite, 6-sulphatoxymelatonin (6-SM), in the patients' urine, and immunohistochemistry in the hypothalamus, the basal nucleus of Meynert (NbM), and the pedunculopontine tegmental nucleus (PPN) in four autopsy cases. RESULTS: Sleep-wakefulness rhythms were disturbed in patients with CS, and these disturbances seemed to be related to a reduced urinary excretion of 6-SM. In addition, although the hypothalamic nuclei were comparatively preserved, acetylcholine neurons (AchNs) were severely decreased in the NbM and PPN. CONCLUSIONS: AchNs modulate both arousal and rapid eye movement sleep, and selective lesions of AchNs in the PPN and/or NbM in combination with disturbed melatonin metabolism might be involved in the sleep disorders in CS.
BACKGROUND:Cockayne syndrome (CS) is a genetic disorder caused by deficient nucleotide excision repair. Patients with CS exhibit progeroid features, developmental delay, and various neurological disorders; they are also known to suffer from sleep problems, which have never been investigated in detail. OBJECTIVE: The aim of this study is to investigate the pathogenesis of sleep disorders in patients with CS. METHODS: We performed a questionnaire survey of the families of patients with CS, enzyme-linked immunosorbent analyses of the melatonin metabolite, 6-sulphatoxymelatonin (6-SM), in the patients' urine, and immunohistochemistry in the hypothalamus, the basal nucleus of Meynert (NbM), and the pedunculopontine tegmental nucleus (PPN) in four autopsy cases. RESULTS: Sleep-wakefulness rhythms were disturbed in patients with CS, and these disturbances seemed to be related to a reduced urinary excretion of 6-SM. In addition, although the hypothalamic nuclei were comparatively preserved, acetylcholine neurons (AchNs) were severely decreased in the NbM and PPN. CONCLUSIONS:AchNs modulate both arousal and rapid eye movement sleep, and selective lesions of AchNs in the PPN and/or NbM in combination with disturbed melatonin metabolism might be involved in the sleep disorders in CS.
Authors: Omotayo B Ilesanmi; Afolabi C Akinmoladun; Olanrewaju Sam Olayeriju; Ibrahim Olabayode Saliu; M Tolulope Olaleye; Afolabi A Akindahunsi Journal: Afr J Tradit Complement Altern Med Date: 2017-06-05