Narcolepsy is a common cause of chronic sleepiness distinguished by intrusions into wakefulness of physiological aspects of rapid eye movement sleep such as cataplexy and hallucinations. Recent advances provide compelling evidence that narcolepsy may be a neurodegenerative or autoimmune disorder resulting in a loss of hypothalamic neurons containing the neuropeptide orexin (also known as hypocr...

A study by Zhang et al. in this issue of Neuron reveals a novel mechanism of control of vestibular motor functions by the orexin (hypocretin) system in the perifornical/LH area through the lateral vestibular nucleus in the brainstem. This knowledge provides new insights into the understanding of brain circuitry that controls motor functions and diseases/conditions related to impairments in this...

A new orexigenic peptide called hypocretin (orexin) has recently been described in neurons of the lateral hypothalamus and perifornical area. The medial and lateral hypothalamus have been loosely called satiety and feeding centers of the brain, respectively. Approximately one-third of all medial and lateral hypothalamic neurons tested, but not hippocampal neurons, show a striking nanomolar sens...

Hypocretin (orexin) is synthesized by neurons in the lateral hypothalamus and has been reported to increase food intake and regulate the neuroendocrine system. In the present paper, long descending axonal projections that contain hypocretin were found that innervate all levels of the spinal cord from cervical to sacral segments, as studied in mouse, rat, and human spinal cord and not previously...

OBJECTIVE To investigate whether neuronal activity-regulated pentraxin (Narp) colocalizes with hypocretin (Hcrt or orexin) in the normal human brain and to determine if Narp staining is lost in the narcoleptic human brain. BACKGROUND Human narcolepsy is characterized by a loss of the peptide hypocretin in the hypothalamus. This loss could result from the degeneration of neurons containing hyp...

The neuropeptide orexin (also known as hypocretin) is hypothesized to play a critical role in the regulation of sleep-wake behavior. Lack of orexin produces narcolepsy, which is characterized by poor maintenance of wakefulness and intrusions of rapid eye movement (REM) sleep or REM sleep-like phenomena into wakefulness. Orexin neurons heavily innervate many aminergic nuclei that promote wakeful...

AL. REINFORCES PRIOR WORK THAT SUGGESTS THAT HYPOCRETIN (HCRT, ALSO KNOWN AS OREXIN) ADMINISTRATION WILL BE AN EFFECTIVE TREATMENT FOR HUMAN NARCOLEPSY. Most human narcolepsy is caused by a loss of hypocretin neurons.1-3 That finding suggested that Hcrt administration might be an effective treatment for narcolepsy. Work in our laboratory showed that intravenous (IV) Hcrt administration reduced ...

A recent publication suggested that hypocretin (Hcrt, orexin) may mediate the neuropathological process leading to Alzheimer's disease (AD) and that antagonism of hypocretin receptors decreases this process. Narcoleptics have an approximately 90% loss of Hcrt neurons and commensurate reductions in the levels of Hcrt in their cerebrospinal fluid beginning at disease onset, usually before the age...