title: Melatonin alterations and brain acetylcholine lesions in sleep disorders in Cockayne syndrome.
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.
authors: 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.
authors: Yumi
authors: Y
authors: Okoshi
authors: Department of Pediatrics, Tokyo Metropolitan Fuchu Medical Center for the Disabled, Tokyo, Japan.
authors: Naoyuki
authors: N
authors: Tanuma
authors: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan.
authors: Rie
authors: R
authors: Miyata
authors: Department of Brain Development and Neural Regeneration, Tokyo Metropolitan Institute of Medical Science, Tokyo, Japan. Electronic address: hayashi-ms@igakuken.or.jp.
authors: Masaharu
authors: M
authors: Hayashi
mesh_terms: D000109:Acetylcholine / Q000378:metabolism*; D000293:Adolescent; D000328:Adult; D000975:Antioxidants / Q000627:therapeutic use*; D001921:Brain / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D003057:Cockayne Syndrome / Q000150:complications*; D005260:Female; D006801:Humans; D008297:Male; D008550:Melatonin / Q000031:analogs & derivatives / Q000378:metabolism / Q000627:therapeutic use* / Q000652:urine; D046529:Microscopy, Electron, Transmission; D009419:Nerve Tissue Proteins / Q000378:metabolism; D012893:Sleep Wake Disorders / Q000188:drug therapy / Q000209:etiology / Q000473:pathology; D011795:Surveys and Questionnaires; D055815:Young Adult
chemical_list: D000975:Antioxidants; D009419:Nerve Tissue Proteins; C054513:6-sulfatoxymelatonin; D008550:Melatonin; D000109:Acetylcholine
keywords: Acetylcholine; Cockayne syndrome; Hypothalamus; Immunohistochemistry; Melatonin; Sleep disorders