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      Reduced Number of Hypocretin Neurons in Human Narcolepsy

      , , , , , , ,

      Neuron

      Elsevier BV

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          Abstract

          Murine and canine narcolepsy can be caused by mutations of the hypocretin (Hcrt) (orexin) precursor or Hcrt receptor genes. In contrast to these animal models, most human narcolepsy is not familial, is discordant in identical twins, and has not been linked to mutations of the Hcrt system. Thus, the cause of human narcolepsy remains unknown. Here we show that human narcoleptics have an 85%-95% reduction in the number of Hcrt neurons. Melanin-concentrating hormone (MCH) neurons, which are intermixed with Hcrt cells in the normal brain, are not reduced in number, indicating that cell loss is relatively specific for Hcrt neurons. The presence of gliosis in the hypocretin cell region is consistent with a degenerative process being the cause of the Hcrt cell loss in narcolepsy.

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          Author and article information

          Journal
          Neuron
          Neuron
          Elsevier BV
          08966273
          September 2000
          September 2000
          : 27
          : 3
          : 469-474
          Article
          10.1016/S0896-6273(00)00058-1
          11055430
          © 2000

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