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VOLUME 36, ISSUE 01

SUPRACHIASMATIC NUCLEUS IN HUNTINGTON'S DISEASE
Suprachiasmatic Nucleus Neuropeptide Expression in Patients with Huntington's Disease

http://dx.doi.org/10.5665/sleep.2314

Daniel J. van Wamelen, MD1,2; N. Ahmad Aziz, MD, PhD2; Jasper J. Anink, BSc1; Robin van Steenhoven, BSc1; Debora Angeloni, PhD3; Franco Fraschini, PhD4; Ralf Jockers, PhD5,7; Raymund A. C. Roos, MD, PhD2; Dick F. Swaab, MD, PhD1

1Netherlands Institute for Neuroscience, an Institute of the Royal Netherlands Academy of Arts and Sciences, Amsterdam, the Netherlands; 2Department of Neurology, Leiden University Medical Center, Leiden, the Netherlands; 3Scuola Superiore Sant'Anna and Institute of Clinical Physiology, Pisa, Italy; 4Department of Medical Biotechnology and Translational Medicine, University of Milano, Milan, Italy; 5Inserm, U1016, Institut Cochin, Paris, France; 6CNRS, UMR 8104, Paris, France; 7Université Paris Descartes, Sorbonne Paris Cite, Paris, France



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Study 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.

Design:

Postmortem cohort study.

Patients:

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.

Measurements and 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.

Citation:

van Wamelen DJ; Aziz NA; Anink JJ; van Steenhoven R; Angeloni D; Fraschini F; Jockers R; Roos RAC; Swaab DF. Suprachiasmatic nucleus neuropeptide expression in patients with Huntington's disease. SLEEP 2013;36(1):117–125.

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