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Orexin loss in Huntington's disease.

Petersén, Åsa LU ; Gil, Joana LU ; Maat-Schieman, Marion L C; Björkqvist, Maria LU ; Tanila, Heikki; Araújo, Ines M; Smith, Ruben LU ; Popovic, Natalija LU ; Wierup, Nils LU and Norlén, Per LU , et al. (2005) In Human Molecular Genetics 14(1). p.39-47
Abstract
Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. Mutant huntingtin forms intracellular aggregates and is associated with neuronal death in select brain regions. The most studied mouse model (R6/2) of HD replicates many features of the disease, but has been reported to exhibit only very little neuronal death. We describe for the first time a dramatic atrophy and loss of orexin neurons in the lateral hypothalamus of R6/2 mice. Importantly, we also found a significant atrophy and loss of orexin neurons in Huntington patients. Like animal models and patients with impaired orexin function, the R6/2 mice were narcoleptic. Both... (More)
Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. Mutant huntingtin forms intracellular aggregates and is associated with neuronal death in select brain regions. The most studied mouse model (R6/2) of HD replicates many features of the disease, but has been reported to exhibit only very little neuronal death. We describe for the first time a dramatic atrophy and loss of orexin neurons in the lateral hypothalamus of R6/2 mice. Importantly, we also found a significant atrophy and loss of orexin neurons in Huntington patients. Like animal models and patients with impaired orexin function, the R6/2 mice were narcoleptic. Both the number of orexin neurons in the lateral hypothalamus and the levels of orexin in the cerebrospinal fluid were reduced by 72% in end-stage R6/2 mice compared with wild-type littermates, suggesting that orexin could be used as a biomarker reflecting neurodegeneration. Our results show that the loss of orexin is a novel and potentially very important pathology in HD. (Less)
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published
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Human Molecular Genetics
volume
14
issue
1
pages
39 - 47
publisher
Oxford University Press
external identifiers
  • wos:000226199300004
  • pmid:15525658
  • scopus:19944427749
ISSN
0964-6906
DOI
10.1093/hmg/ddi004
language
English
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yes
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30f1903e-82ac-4e3d-9469-05207c0351c9 (old id 130965)
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http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15525658&dopt=Abstract
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2007-07-06 07:13:27
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2017-11-19 03:25:48
@article{30f1903e-82ac-4e3d-9469-05207c0351c9,
  abstract     = {Huntington's disease (HD) is a devastating neurodegenerative disorder caused by an expanded CAG repeat in the gene encoding huntingtin, a protein of unknown function. Mutant huntingtin forms intracellular aggregates and is associated with neuronal death in select brain regions. The most studied mouse model (R6/2) of HD replicates many features of the disease, but has been reported to exhibit only very little neuronal death. We describe for the first time a dramatic atrophy and loss of orexin neurons in the lateral hypothalamus of R6/2 mice. Importantly, we also found a significant atrophy and loss of orexin neurons in Huntington patients. Like animal models and patients with impaired orexin function, the R6/2 mice were narcoleptic. Both the number of orexin neurons in the lateral hypothalamus and the levels of orexin in the cerebrospinal fluid were reduced by 72% in end-stage R6/2 mice compared with wild-type littermates, suggesting that orexin could be used as a biomarker reflecting neurodegeneration. Our results show that the loss of orexin is a novel and potentially very important pathology in HD.},
  author       = {Petersén, Åsa and Gil, Joana and Maat-Schieman, Marion L C and Björkqvist, Maria and Tanila, Heikki and Araújo, Ines M and Smith, Ruben and Popovic, Natalija and Wierup, Nils and Norlén, Per and Li, Jia-Yi and Roos, Raymund Ac and Sundler, Frank and Mulder, Hindrik and Brundin, Patrik},
  issn         = {0964-6906},
  language     = {eng},
  number       = {1},
  pages        = {39--47},
  publisher    = {Oxford University Press},
  series       = {Human Molecular Genetics},
  title        = {Orexin loss in Huntington's disease.},
  url          = {http://dx.doi.org/10.1093/hmg/ddi004},
  volume       = {14},
  year         = {2005},
}