title: Neuropeptide alterations in the infundibular nucleus of Huntington's disease patients.
abstract: Data from transgenic mouse models of Huntington's disease (HD) suggest that dysfunction of the hypothalamic infundibular nucleus (INF) (in rodents, the arcuate nucleus) may contribute to unintended weight loss and insatiable appetite among HD patients. Using post-mortem paraffin-embedded tissue, we assessed the total number of INF neurones by thionin staining and four major regulatory neuropeptides in the INF of HD patients by immunocytochemistry and in situ hybridisation. In HD patients, the total number of neurones in the INF was unchanged compared to control subjects (P = 0.92), whereas it contained over 30% less neuropeptide Y-immunoreactive (IR) neurones (P = 0.016), as well as reduced peptide levels, in fibres to the paraventricular and ventromedial nucleus (P = 0.003, P = 0.005, respectively). Conversely, neuropeptide Y mRNA expression levels were increased three-fold (P = 0.047). No changes were observed in the number of neurones immunoreactive for α-melanocyte-stimulating hormone, agouti-related peptide, and cocaine- and amphetamine-regulated transcript (P ≥ 0.17). Our findings suggest changes in the pathology of the INF neuropeptide Y-expressing neurones in HD patients without changes in other (an)orexigenic neuropeptides and without neuronal cell loss. These findings indicate that unintended weight loss in patients suffering from this disease may be partly a result of neuropeptidergic alterations in the hypothalamic infundibular nucleus.
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: D J
authors.initials: DJ
authors.lastname: van Wamelen
authors.forename: N A
authors.initials: NA
authors.lastname: Aziz
authors.forename: J J
authors.initials: JJ
authors.lastname: Anink
authors.forename: R A C
authors.initials: RA
authors.lastname: Roos
authors.forename: D F
authors.initials: DF
authors.lastname: Swaab
mesh_terms: D000328:Adult; D000368:Aged; D001111:Arcuate Nucleus of Hypothalamus / Q000378:metabolism* / Q000473:pathology; D001344:Autopsy; D016022:Case-Control Studies; D005260:Female; D006801:Humans; D006816:Huntington Disease / Q000378:metabolism* / Q000473:pathology*; D007150:Immunohistochemistry; D008297:Male; D008875:Middle Aged; D009474:Neurons / Q000378:metabolism / Q000473:pathology; D009478:Neuropeptide Y / Q000378:metabolism; D009479:Neuropeptides / Q000378:metabolism*; D000521:alpha-MSH / Q000378:metabolism
chemical_list: D009478:Neuropeptide Y; D009479:Neuropeptides; D000521:alpha-MSH