Mice deficient in the interferon type I receptor have reduced REM sleep and altered hypothalamic hypocretin, prolactin and 2',5'-oligoadenylate synthetase expression.
We report that mice with a targeted null mutation in the interferon type I receptor (IFN-RI), which cannot respond to such IFNs as IFNalpha and IFNbeta, have a 30% reduction in time spent in spontaneous rapid eye movement sleep (REMS) as a consequence of a reduced number of REMS episodes. Time spent in nonrapid eye movement sleep (NREMS) was essentially unaltered in IFN-RI knockouts (KOs) compared to 129 SvEv controls. Body temperature and locomotor activity were similar in both strains of mice. Hypothalamic expression of mRNAs for molecules previously linked to sleep-wake regulation and an IFN-inducible antiviral gene, 2',5'-oligoadenylate synthetase 1a (OAS), were determined by real-time reverse-transcriptase polymerase chain reaction (RT2-PCR). The level of hypocretin A mRNA was elevated in IFN-RI KO mice compared to 129 SvEv mice, while prolactin mRNA and OAS mRNA levels were suppressed. Vasoactive intestinal peptide (VIP) and corticotropin-releasing hormone (CRH) mRNA levels were unchanged relative to controls. Serum prolactin levels were similar in both strains. Results are consistent with the hypothesis that increased hypocretin and reduced prolactin in the hypothalamus of IFN-RI KO mice are responsible for their reduced REMS. In addition, the reduced OAS expression may result in modulation of prolactin receptor signaling and thus contribute to suppression of REMS.
Bohnet
S G
SG
Department of VCAPP College of Veterinary Medicine Washington State University PO Box 646520 Pullman, WA 99164-6520, USA.
Traynor
T R
TR
Majde
J A
JA
Kacsoh
B
B
Krueger
J M
JM
D015088:2',5'-Oligoadenylate Synthetase / Q000378:metabolism*; D000704:Analysis of Variance; D000818:Animals; D004569:Electroencephalography / Q000379:methods; D004576:Electromyography / Q000379:methods; D005786:Gene Expression Regulation / Q000235:genetics*; D007031:Hypothalamus / Q000201:enzymology / Q000378:metabolism*; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism*; D008297:Male; D051379:Mice; D008815:Mice, Inbred Strains; D018345:Mice, Knockout; D009479:Neuropeptides / Q000378:metabolism*; D064446:Orexin Receptors; D000068797:Orexins; D011388:Prolactin / Q000097:blood*; D012333:RNA, Messenger / Q000096:biosynthesis; D043562:Receptors, G-Protein-Coupled; D017471:Receptors, Interferon / Q000172:deficiency* / Q000502:physiology; D018013:Receptors, Neuropeptide; D020133:Reverse Transcriptase Polymerase Chain Reaction / Q000379:methods; D012895:Sleep, REM / Q000235:genetics*; D013997:Time Factors
D047908:Intracellular Signaling Peptides and Proteins; D009479:Neuropeptides; D064446:Orexin Receptors; D000068797:Orexins; D012333:RNA, Messenger; D043562:Receptors, G-Protein-Coupled; D017471:Receptors, Interferon; D018013:Receptors, Neuropeptide; D011388:Prolactin; D015088:2',5'-Oligoadenylate Synthetase