title: Interleukin 1beta enhances non-rapid eye movement sleep and increases c-Fos protein expression in the median preoptic nucleus of the hypothalamus.
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.
authors.affiliation: Department of Psychology, University of California, Los Angeles, California, USA.
authors.forename: F C
authors.initials: FC
authors.lastname: Baker
authors.forename: S
authors.initials: S
authors.lastname: Shah
authors.forename: D
authors.initials: D
authors.lastname: Stewart
authors.forename: C
authors.initials: C
authors.lastname: Angara
authors.forename: H
authors.initials: H
authors.lastname: Gong
authors.forename: R
authors.initials: R
authors.lastname: Szymusiak
authors.forename: M R
authors.initials: MR
authors.lastname: Opp
authors.forename: D
authors.initials: D
authors.lastname: McGinty
mesh_terms: D000818:Animals; D001831:Body Temperature / Q000187:drug effects; D002452:Cell Count; D007150:Immunohistochemistry; D007276:Injections, Intraventricular; D007375:Interleukin-1 / Q000494:pharmacology*; D008297:Male; D011301:Preoptic Area / Q000166:cytology / Q000187:drug effects / Q000378:metabolism*; D016760:Proto-Oncogene Proteins c-fos / Q000096:biosynthesis*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM / Q000187:drug effects*
chemical_list: D007375:Interleukin-1; D016760:Proto-Oncogene Proteins c-fos