HD Lighthouse Contributing Editor's Comment: Huntington's Disease causes the same kind of cell death in the hypothalamus that is found in narcolepsy. This explains the excessive sleeping of people who have the disease.
--Marsha L. Miller, Ph.D.
Posted to the HDL: 07 Nov 2004

Orexin loss in Huntington's disease.

Huntington's disease 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 Huntington's disease 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 to wild-type littermates, suggesting that orexin could be used as a biomarker reflecting neurodegeneration. Our results show that loss of orexin is a novel and potentially very important pathology in Huntington's disease. # # #

Source: Hum Mol Genet. 2004 Nov 3

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