Interleukin 1beta enhances non-rapid eye movement sleep and increases c-Fos protein expression in the median preoptic nucleus of the hypothalamus.

Publication Type Academic Article
Authors Baker F, Shah S, Stewart D, Angara C, Gong H, Szymusiak R, Opp M, McGinty D
Journal Am J Physiol Regul Integr Comp Physiol
Volume 288
Issue 4
Pagination R998-R1005
Date Published 12/16/2004
ISSN 0363-6119
Keywords Interleukin-1, Preoptic Area, Proto-Oncogene Proteins c-fos, Sleep, REM
Abstract Interleukin 1beta (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 area (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 (10 ng) at dark onset spent significantly more time in NREM sleep 4-5 h after injection. This increase in NREM sleep was associated with increased numbers of Fos-IR neurons in the MnPN, but not in the VLPO. Fos IR in the rostral MnPN was significantly increased 2 h post IL-1 injection, although the percentage of NREM sleep in the preceding 2 h was the same as controls. Fos IR was also increased in the extended VLPO 2 h postinjection. Finally, Fos IR in the MnPN did not differ significantly between IL-1 and vehicle-treated rats that had been sleep deprived for 2 h 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.
DOI 10.1152/ajpregu.00615.2004
PubMed ID 15604300
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