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Acta Neuropathologica
Published in: Acta Neuropathologica 6/2010

01-12-2010 | Original Paper

Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses

Authors: Sanaz Gabery, Karen Murphy, Kristofer Schultz, Clement T. Loy, Elizabeth McCusker, Deniz Kirik, Glenda Halliday, Åsa Petersén

Published in: Acta Neuropathologica | Issue 6/2010

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Abstract

Huntington disease (HD) is a fatal neurodegenerative disorder caused by expansion of a CAG repeat in the HD gene. Degeneration concentrating in the basal ganglia has been thought to account for the characteristic psychiatric symptoms, cognitive decline and motor dysfunction. However, the homeostatic control of emotions and metabolism are disturbed early in HD, and focused studies have identified a loss of orexin (hypocretin) neurons in the lateral hypothalamus in HD patients. There has been limited assessment of other hypothalamic cell populations that may be involved. In this study, we quantified the neuropeptide-expressing hypothalamic neurons known to regulate metabolism and emotion in patients with HD compared to healthy controls using unbiased stereological methods. We confirmed the loss of orexin-expressing neurons in HD and revealed substantial differences in the peptide expression of other neuronal populations in the same patients. Both oxytocin- and vasopressin-expressing neurons were decreased by 45 and 24%, respectively, while the number of cocaine- and amphetamine-regulated transcript (CART)-expressing neurons was increased by 30%. The increased expression of CART in the hypothalamus is consistent with a previous study showing increased CART levels in cerebrospinal fluid from HD patients. There was no difference in the numbers of neuropeptide Y-expressing neurons. These results show significant and specific alterations in the peptide expression of hypothalamic neurons known to regulate metabolism and emotion. They may be important in the development of psychiatric symptoms and metabolic disturbances in HD, and may provide potential targets for therapeutic interventions.
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Metadata
Title
Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses
Authors
Sanaz Gabery
Karen Murphy
Kristofer Schultz
Clement T. Loy
Elizabeth McCusker
Deniz Kirik
Glenda Halliday
Åsa Petersén
Publication date
01-12-2010
Publisher
Springer-Verlag
Published in
Acta Neuropathologica / Issue 6/2010
Print ISSN: 0001-6322
Electronic ISSN: 1432-0533
DOI
https://doi.org/10.1007/s00401-010-0742-6

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