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      From The Cover: Orexin peptides prevent cataplexy and improve wakefulness in an orexin neuron-ablated model of narcolepsy in mice

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      Proceedings of the National Academy of Sciences

      Proceedings of the National Academy of Sciences

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          Abstract

          Narcolepsy-cataplexy is a neurological disorder associated with the inability to maintain wakefulness and abnormal intrusions of rapid eye movement sleep-related phenomena into wakefulness such as cataplexy. The vast majority of narcoleptic-cataplectic individuals have low or undetectable levels of orexin (hypocretin) neuropeptides in the cerebrospinal fluid, likely due to specific loss of the hypothalamic orexin-producing neurons. Currently available treatments for narcolepsy are only palliative, symptom-oriented pharmacotherapies. Here, we demonstrate rescue of the narcolepsy-cataplexy phenotype of orexin neuron-ablated mice by genetic and pharmacological means. Ectopic expression of a prepro-orexin transgene in the brain completely prevented cataplectic arrests and other abnormalities of rapid eye movement sleep in the absence of endogenous orexin neurons. Central administration of orexin-A acutely suppressed cataplectic behavioral arrests and increased wakefulness for 3 h. These results indicate that orexin neuron-ablated mice retain the ability to respond to orexin neuropeptides and that a temporally regulated and spatially targeted secretion of orexins is not necessary to prevent narcoleptic symptoms. Orexin receptor agonists would be of potential value for treating human narcolepsy.

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          Most cited references 25

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          Orexins and Orexin Receptors: A Family of Hypothalamic Neuropeptides and G Protein-Coupled Receptors that Regulate Feeding Behavior

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            • Article: not found

            Efficient selection for high-expression transfectants with a novel eukaryotic vector

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              A mutation in a case of early onset narcolepsy and a generalized absence of hypocretin peptides in human narcoleptic brains.

              We explored the role of hypocretins in human narcolepsy through histopathology of six narcolepsy brains and mutation screening of Hcrt, Hcrtr1 and Hcrtr2 in 74 patients of various human leukocyte antigen and family history status. One Hcrt mutation, impairing peptide trafficking and processing, was found in a single case with early onset narcolepsy. In situ hybridization of the perifornical area and peptide radioimmunoassays indicated global loss of hypocretins, without gliosis or signs of inflammation in all human cases examined. Although hypocretin loci do not contribute significantly to genetic predisposition, most cases of human narcolepsy are associated with a deficient hypocretin system.
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                Author and article information

                Journal
                Proceedings of the National Academy of Sciences
                Proceedings of the National Academy of Sciences
                Proceedings of the National Academy of Sciences
                0027-8424
                1091-6490
                March 30 2004
                March 30 2004
                March 16 2004
                March 30 2004
                : 101
                : 13
                : 4649-4654
                Article
                10.1073/pnas.0400590101
                384801
                15070772
                © 2004
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