Submitted on September 9, 2004
Accepted on December 14, 2004
Interleukin 1
enhances non-rapid eye movement sleep and increases c-Fos protein expression in the median preoptic nucleus of the hypothalamus
F. C Baker1, S. Shah2, D. Stewart3, C. Angara4, H. Gong4, R. Szymusiak3, M. R Opp5, and D. McGinty6*
1 Department of Psychology, University of California, Los Angeles, CA, USA; Brain Function Research Unit, School of Physiology, University of the Witwatersrand, Johannesburg, South Africa
2 Research Service, V. A. Greater Los Angeles Healthcare System, North Hills, CA, USA
3 Department of Medicine, University of California, Los Angeles, CA, USA; Research Service, V. A. Greater Los Angeles Healthcare System, North Hills, CA, USA
4 Department of Psychology, University of California, Los Angeles, CA, USA
5 Department of Anesthesiology, University of Michigan School of Medicine, Ann Arbor, MI, USA
6 Department of Psychology, University of California, Los Angeles, CA, USA; Research Service, V. A. Greater Los Angeles Healthcare System, North Hills, CA, USA
* To whom correspondence should be addressed. E-mail: dmcginty{at}ucla.edu.
Interleukin 1
(IL-1) is a key mediator of the acute phase response in an infected host and acts centrally to coordinate responses to an immune challenge, such as fever and increased non-rapid eye movement (NREM) sleep. The preoptic/anterior hypothalamus (POA) is a primary sleep regulatory center in the brain: the ventrolateral POA (VLPO) and median preoptic nucleus (MnPN) each contain high numbers of c-Fos protein
immunoreactive (IR) neurons after sleep but not after waking. We hypothesized that IL-1 mediates increased NREM sleep through activation of these sleep-active sites. Rats
injected intracerebroventricularly with IL-1 (10ng) at dark onset spent significantly more time in NREM sleep four-five hours after injection. This increase in NREM sleep was associated with increased numbers of Fos IR neurons in the MnPN, but not in VLPO. Fos IR in the rostral MnPN was significantly increased two hours post IL-1 injection, although percentage NREM sleep in the preceding two hours was the same as controls. Fos IR was also increased in the extended VLPO two hours postinjection. Finally, Fos IR in the MnPN did not differ significantly between IL-1 and vehicle-treated rats that
had been sleep deprived for two hours postinjection but it was increased in VLPO core. Taken together, these results suggest that Fos IR in the MnPN after IL-1 is not
independent of behavioral state, and may require some threshold amount of sleep for its expression. Our results support a hypothesis that IL-1 enhances NREM sleep, in part, through activation of neurons in the MnPN of the hypothalamus.
