![]() To examine whether the narcolepsy-cataplexy phenotype of orexin neuron-ablated mice could be rescued by ectopic production of orexin peptides, we produced transgenic mice that overexpress a prepro-orexin transgene under the control of a β-actin/cytomegalovirus hybrid promoter ( CAG/ orexin-transgenic mice). Genetic Rescue of Narcolepsy in Orexin Neuron-Ablated Mice. Orexin receptor agonists would be of potential value for treating human narcolepsy. 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. Central administration of orexin-A acutely suppressed cataplectic behavioral arrests and increased wakefulness for 3 h. 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. Here, we demonstrate rescue of the narcolepsy-cataplexy phenotype of orexin neuron-ablated mice by genetic and pharmacological means. Currently available treatments for narcolepsy are only palliative, symptom-oriented pharmacotherapies. 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. 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. ![]()
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