HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) Supplemental data All Versions of this Article: 581/2/649    most recent jphysiol.2007.129510v1 Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Zhang, S. Articles by Mignot, E. Search for Related Content PubMed PubMed Citation Articles by Zhang, S. Articles by Mignot, E. Related Collections Neuroscience

¹ Psychiatry and Behavioural Sciences, Stanford University, Palo Alto, CA, USA
² VA Palo Alto Health Care System, Palo Alto, CA, USA
³ Institute of Basic Medical Sciences, University of Tsukuba, Ibaraki, Japan
⁴ Howard Hughes Medical Institute, Stanford, CA, USA

Recent population studies have identified important interrelationships between sleep duration and body weight regulation. The hypothalamic hypocretin/orexin neuropeptide system is able to influence each of these. Disruption of the hypocretin system, such as occurs in narcolepsy, leads to a disruption of sleep and is often associated with increased body mass index. We examined the potential interrelationship between the hypocretin system, metabolism and sleep by measuring locomotion, feeding, drinking, body temperature, sleep/wake and energy metabolism in a mouse model of narcolepsy (ataxin-ablation of hypocretin-expressing neurons). We found that locomotion, feeding, drinking and energy expenditure were significantly reduced in the narcoleptic mice. These mice also exhibited severe sleep/wake fragmentation. Upon awakening, transgenic and control mice displayed a similar rate of increase in locomotion and food/water intake with time. A lack of long wake episodes partially or entirely explains observed differences in overall locomotion, feeding and drinking in these transgenic mice. Like other parameters, energy expenditure also rose and fell depending on the sleep/wake status. Unlike other parameters, however, energy expenditure in control mice increased upon awakening at a greater rate than in the narcoleptic mice. We conclude that the profound sleep/wake fragmentation is a leading cause of the reduced locomotion, feeding, drinking and energy expenditure in the narcoleptic mice under unperturbed conditions. We also identify an intrinsic role of the hypocretin system in energy expenditure that may not be dependent on sleep/wake regulation, locomotion, or food intake. This investigation illustrates the need for coordinated study of multiple phenotypes in mouse models with altered sleep/wake patterns.

(Received 31 January 2007; accepted after revision 16 March 2007; first published online 22 March 2007)
Corresponding author E. Mignot: Center for Narcolepsy, Stanford University, 701B Welch Road, Room 145, Palo Alto CA 94304-5742, USA.  Email: mignot{at}stanford.edu

This article has been cited by other articles:

				J. M. Zeitzer, C. L. Buckmaster, D. M. Lyons, and E. Mignot Increasing length of wakefulness and modulation of hypocretin-1 in the wake-consolidated squirrel monkey Am J Physiol Regulatory Integrative Comp Physiol, October 1, 2007; 293(4): R1736 - R1742. [Abstract] [Full Text] [PDF]