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Pathogenic mechanisms
A22 Hypothalamic changes in Huntington's disease
  1. D van Wamelen1,2,
  2. A Aziz1,
  3. L Shan1,3,
  4. J Anink1,
  5. R A C Roos2,
  6. D Swaab1
  1. 1Netherlands Institute for Neuroscience, Amsterdam, The Netherlands
  2. 2Department of Neurology, Leiden University Medical Centre, Leiden, The Netherlands
  3. 3Institute of Neuroscience, Zhejiang University School of Medicine, Hangzhou, China


Background In recent years it has become increasingly clear that the hypothalamus might be affected in Huntington's disease (HD), and that this may underlie many features in this disease. Research on the hypothalamus itself in HD patients, however, has so far been limited.

Aims To systematically assess four major hypothalamic nuclei, the suprachiasmatic (SCN), paraventricular (PVN), infundibular (INF) and tuberomamillary nucleus (TMN) for changes in the level of neurotransmitters/neuromodulators in these nuclei.

Methods We used a combination of quantitative immunohistochemistry and radioactive in situ hybridisation techniques on post-mortem, paraffin embedded, hypothalamic tissue in HD patients (n=9) and well matched control subjects (n=9).

Results In the SCN, the number of vasopressin and vasoactive intestinal polypeptide expressing neurons was decreased in HD patients (p=0.03 and 0.001, respectively). Numbers of melatonin 2 receptor expressing neurons were unchanged (p=0.32). In the PVN, the number of corticotropin releasing hormone expressing neurons was unchanged (p=0.55), as were thyroid stimulating hormone mRNA levels (p=0.21). In the INF, the number of neuropeptide Y expressing neurons was decreased in HD patients (p=0.01), the number of neurons expressing α-melanocyte stimulating hormone, agouti related peptide and cocaine and amphetamine regulated transcript was unchanged (p=0.20, p=0.32 and p=0.20, respectively). In the TMN, mRNA levels of histidine decarboxylase, the rate limiting enzyme for histamine production, were increased in HD patients (p=0.05).

Conclusions These results show that the hypothalamus in HD is severely affected, contributing to several features in patients, such as circadian rhythm disturbances, weight loss and cognitive decline. Furthermore, our findings may provide a basis for rational therapeutic strategies aimed at ameliorating these symptoms.

  • hypothalamus
  • immunohistochemistry
  • quantitative in situ hybridisation

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