[The neurophysiology of cataplexy].
Cataplexy and excessive daytime sleepiness are the leading symptoms of narcolepsy. Electrophysiological studies in humans do not show a clear association between cataplexy and rapid eye movement (REM) sleep. Even a decrement of the H reflex is not specific for cataplexy and may be caused by unspecific triggers such as coughing. Cholinomimetics, which may induce status cataplecticus, do not influence REM sleep, thus evidencing a REM-independent mechanism. Recent studies demonstrate a lack of the neuropeptide hypocretin in the CSF of narcoleptics. Hypocretin controls wakefulness and the motor and autonomous systems. In hypocretin-1 and -2 knockout mice, sudden stops of motor activity could be observed in emotional situations that were accompanied by sudden shifts from wakefulness to REM sleep and could be terminated by application of anticataplectic medication. The lack of hypocretin not only causes a noradrenergic-cholinergic imbalance in the midbrain but also influences motoneurons directly by juxtacellular hypocretin-containing membranes. Intravenous application of hypocretin in a dog with hypocretin deficiency in the CSF caused a dose-dependent decrease of cataplexies. An understanding of the neuronal mechanisms responsible for cataplexies is essential for the development of new anticataplectic medications.
Mayer
G
G
Hephata-Klinik, Schwalmstadt-Treysa. geert.mayer@hephata.com
D000818:Animals; D001921:Brain / Q000503:physiopathology*; D002385:Cataplexy / Q000503:physiopathology*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D051379:Mice; D008959:Models, Neurological; D009290:Narcolepsy / Q000503:physiopathology*; D009479:Neuropeptides / Q000378:metabolism*; D009482:Neurophysiology / Q000379:methods; D000068797:Orexins; D012895:Sleep, REM
C000596229:HCRT protein, human; D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins