title: Suprachiasmatic nucleus neuropeptide expression in patients with Huntington's Disease.
abstract: OBJECTIVE
  To study whether sleep and circadian rhythm disturbances in patients with Huntington's disease (HD) arise from dysfunction of the body's master clock, the hypothalamic suprachiasmatic nucleus.
  
  
  METHODS
  Postmortem cohort study.
  
  
  METHODS
  Eight patients with HD and eight control subjects matched for sex, age, clock time and month of death, postmortem delay, and fixation time of paraffin-embedded hypothalamic tissue.
  
  
  RESULTS
  Using postmortem paraffin-embedded tissue, we assessed the functional integrity of the suprachiasmatic nucleus in patients with HD and control subjects by determining the expression of two major regulatory neuropeptides, vasoactive intestinal polypeptide and arginine vasopressin. Additionally, we studied melatonin 1 and 2 receptor expression. Compared with control subjects, the suprachiasmatic nucleus contained 85% fewer neurons immunoreactive for vasoactive intestinal polypeptide and 33% fewer neurons for arginine vasopressin in patients with HD (P = 0.002 and P = 0.027). The total amount of vasoactive intestinal polypeptide and arginine vasopressin messenger RNA was unchanged. No change was observed in the number of melatonin 1 or 2 receptor immunoreactive neurons.
  
  
  CONCLUSIONS
  These findings indicate posttranscriptional neuropeptide changes in the suprachiasmatic nucleus of patients with HD, and suggest that sleep and circadian rhythm disorders in these patients may at least partly arise from suprachiasmatic nucleus dysfunction.
authors.affiliation: Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands. D.J.van_Wamelen@lumc.nl
authors.forename: Daniel J
authors.initials: DJ
authors.lastname: van Wamelen
authors.forename: N Ahmad
authors.initials: NA
authors.lastname: Aziz
authors.forename: Jasper J
authors.initials: JJ
authors.lastname: Anink
authors.forename: Robin
authors.initials: R
authors.lastname: van Steenhoven
authors.forename: Debora
authors.initials: D
authors.lastname: Angeloni
authors.forename: Franco
authors.initials: F
authors.lastname: Fraschini
authors.forename: Ralf
authors.initials: R
authors.lastname: Jockers
authors.forename: Raymund A C
authors.initials: RA
authors.lastname: Roos
authors.forename: Dick F
authors.initials: DF
authors.lastname: Swaab
mesh_terms: D001127:Arginine Vasopressin / Q000378:metabolism; D021081:Chronobiology Disorders / Q000150:complications / Q000378:metabolism*; D002940:Circadian Rhythm; D015331:Cohort Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000150:complications / Q000378:metabolism*; D007031:Hypothalamus / Q000378:metabolism; D017403:In Situ Hybridization / Q000379:methods; D008297:Male; D009479:Neuropeptides / Q000378:metabolism*; D012893:Sleep Wake Disorders / Q000150:complications / Q000378:metabolism*; D013493:Suprachiasmatic Nucleus / Q000378:metabolism*; D014660:Vasoactive Intestinal Peptide / Q000378:metabolism
chemical_list: D009479:Neuropeptides; D001127:Arginine Vasopressin; D014660:Vasoactive Intestinal Peptide