mRNA expression in mouse hypothalamus and basal forebrain during influenza infection: a novel model for sleep regulation.
After influenza infection, C57BL/6J mice develop increased slow-wave sleep (SWS) during the dark phase of the day-night cycle, whereas BALB/cByJ mice develop decreased SWS during the light phase. A previous analysis of CXB recombinant inbred mice revealed a quantitative trait locus (QTL) designated Srilp (sleep response to influenza, light phase) that was related to expression of the BALB/cByJ sleep phenotype. Srilp was localized to the 10- to 12-cM region of mouse Chr 6 between D6Mit74 and D6Mit188. Temt (thioether S-methyltransferase), which is located at region B3 of Chr 6, is a potential candidate gene for Srilp. We evaluated the expression of Temt and other Srilp candidate genes in hypothalamus and basal forebrain of uninfected and influenza-infected C57BL/6J and BALB/cByJ mice. We report here that Temt expression varies significantly with respect to mouse strain, health status, brain region, and day-night phase. C57BL/6J mice show day-night variation in Temt expression in hypothalamus, but BALB/cByJ mice do not. Temt expression in basal forebrain is much higher in C57BL/6J mice than in BALB/cByJ mice. During influenza infection, both C57BL/6J and BALB/cByJ mice show reduced Temt mRNA in basal forebrain at 30 h postinoculation, but expression remains much lower in the BALB/cByJ strain. In contrast, prostaglandin-D-synthase (Ptgds) and lipocalin 2 (Lcn2) mRNA increase in basal forebrain of both strains after influenza infection. Administration of the TEMT inhibitor sinefungin reduces sleep in uninfected BALB/cByJ mice and attenuates influenza-induced sleep enhancement in C57BL/6J mice. These data suggest that strain- and infection-related alterations in sleep may be influenced by Temt expression and perhaps by subsequent effects on prostaglandin metabolism.
Ding
Ming
M
Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois 62794-9616, USA.
Toth
Linda A
LA
D000209:Acute-Phase Proteins / Q000235:genetics / Q000378:metabolism; D000241:Adenosine / Q000031:analogs & derivatives / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D004195:Disease Models, Animal; D007031:Hypothalamus / Q000378:metabolism*; D019746:Intramolecular Oxidoreductases / Q000235:genetics / Q000378:metabolism; D000071068:Lipocalin-2; D054834:Lipocalins; D008297:Male; D008780:Methyltransferases / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008807:Mice, Inbred BALB C; D008810:Mice, Inbred C57BL; D008954:Models, Biological; D015513:Oncogene Proteins / Q000235:genetics / Q000378:metabolism; D009976:Orthomyxoviridae Infections / Q000235:genetics* / Q000503:physiopathology; D016548:Prosencephalon / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism*; D018019:Receptors, Corticotropin-Releasing Hormone / Q000235:genetics / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012890:Sleep / Q000235:genetics / Q000502:physiology*
D000209:Acute-Phase Proteins; C101531:CRF receptor type 2; D000071068:Lipocalin-2; D054834:Lipocalins; D015513:Oncogene Proteins; D012333:RNA, Messenger; D018019:Receptors, Corticotropin-Releasing Hormone; C071332:Lcn2 protein, mouse; D008780:Methyltransferases; C055340:S-adenosyl methionine thioether S-methyltransferase; D019746:Intramolecular Oxidoreductases; C022466:prostaglandin R2 D-isomerase; D000241:Adenosine; C006235:sinefungin