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

Gabery, Sanaz LU ; Murphy, Karen; Schultz, Kristofer LU ; Loy, Clement T; McCusker, Elizabeth; Kirik, Deniz LU ; Halliday, Glenda and Petersén, Åsa LU (2010) In Acta Neuropathologica 120. p.777-788
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... (More)
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. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Acta Neuropathologica
volume
120
pages
777 - 788
publisher
Springer
external identifiers
  • WOS:000284593200008
  • PMID:20821223
  • Scopus:78651085932
ISSN
1432-0533
DOI
10.1007/s00401-010-0742-6
language
English
LU publication?
yes
id
d2b8db8b-5b65-4822-a733-855544275d9f (old id 1688496)
alternative location
http://www.ncbi.nlm.nih.gov/pubmed/20821223?dopt=Abstract
date added to LUP
2010-10-08 08:58:39
date last changed
2016-11-20 04:21:13
@misc{d2b8db8b-5b65-4822-a733-855544275d9f,
  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.},
  author       = {Gabery, Sanaz and Murphy, Karen and Schultz, Kristofer and Loy, Clement T and McCusker, Elizabeth and Kirik, Deniz and Halliday, Glenda and Petersén, Åsa},
  issn         = {1432-0533},
  language     = {eng},
  pages        = {777--788},
  publisher    = {ARRAY(0x80827f0)},
  series       = {Acta Neuropathologica},
  title        = {Changes in key hypothalamic neuropeptide populations in Huntington disease revealed by neuropathological analyses.},
  url          = {http://dx.doi.org/10.1007/s00401-010-0742-6},
  volume       = {120},
  year         = {2010},
}