Running promotes wakefulness and increases cataplexy in orexin knockout mice.
OBJECTIVE
People with narcolepsy and mice lacking orexin/hypocretin have disrupted sleep/wake behavior and reduced physical activity. Our objective was to identify physiologic mechanisms through which orexin deficiency reduces locomotor activity.


METHODS
We examined spontaneous wheel running activity and its relationship to sleep/wake behavior in wild type (WT) and orexin knockout (KO) mice. Additionally, given that physical activity promotes alertness, we also studied whether orexin deficiency reduces the wake-promoting effects of exercise.


RESULTS
Orexin KO mice ran 42% less than WT mice. Their ability to run appeared normal as they initiated running as often as WT mice and ran at normal speeds. However, their running bouts were considerably shorter, and they often had cataplexy or quick transitions into sleep after running. Wheel running increased the total amount of wakefulness in WT and orexin KO mice similarly, however, KO mice continued to have moderately fragmented sleep/wake behavior. Wheel running also doubled the amount of cataplexy by increasing the probability of transitioning into cataplexy.


CONCLUSIONS
Orexin KO mice run significantly less than normal, likely due to sleepiness, imminent cataplexy, or a reduced motivation to run. Orexin is not required for the wake-promoting effects of wheel running given that both WT and KO mice had similar increases in wakefulness with running wheels. In addition, the clear increase in cataplexy with wheel running suggests the possibility that positive emotions or reward can trigger murine cataplexy, similar to that seen in people and dogs with narcolepsy.
Department of Neurology, Beth Israel Deaconess Medical Center, Boston, MA 02115, USA.
Rodrigo A
RA
España
Sarah L
SL
McCormack
Takatoshi
T
Mochizuki
Thomas E
TE
Scammell
D000339:Affect; D000818:Animals; D002385:Cataplexy / Q000378:metabolism*; D004569:Electroencephalography; D004576:Electromyography; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008124:Locomotion; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D009042:Motivation; D009043:Motor Activity; D009479:Neuropeptides / Q000378:metabolism*; D009765:Obesity / Q000378:metabolism; D000068797:Orexins; D012420:Running; D014851:Wakefulness / Q000502:physiology*
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D000068797:Orexins