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Orexin loss in Huntington's disease.

Petersén, Åsa LU ; Gil, Joana LU ; Maat-Schieman, Marion L C ; Björkqvist, Maria LU orcid ; 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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organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Human Molecular Genetics
volume
14
issue
1
pages
39 - 47
publisher
Oxford University Press
external identifiers
  • wos:000226199300004
  • pmid:15525658
  • scopus:19944427749
  • pmid:15525658
ISSN
0964-6906
DOI
10.1093/hmg/ddi004
language
English
LU publication?
yes
id
30f1903e-82ac-4e3d-9469-05207c0351c9 (old id 130965)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15525658&dopt=Abstract
date added to LUP
2016-04-01 11:37:29
date last changed
2023-09-01 00:50:14
@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}},
  doi          = {{10.1093/hmg/ddi004}},
  volume       = {{14}},
  year         = {{2005}},
}