| First Author | Petersén A | Year | 2005 |
| Journal | Hum Mol Genet | Volume | 14 |
| Issue | 1 | Pages | 39-47 |
| PubMed ID | 15525658 | Mgi Jnum | J:136441 |
| Mgi Id | MGI:3796316 | Doi | 10.1093/hmg/ddi004 |
| Citation | Petersen A, et al. (2005) Orexin loss in Huntington's disease. Hum Mol Genet 14(1):39-47 |
| abstractText | 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. |
