Physiol. Genomics AJP: Renal Physiology
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Physiol. Genomics 24: 225-234, 2006. First published January 10, 2006; doi:10.1152/physiolgenomics.00005.2005
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Received 10 January 2005; accepted in final form 12 December 2005.
Physiological Genomics 24:225-234 (2006)
American Physiological Society © 2006 American Physiological Society

mRNA expression in mouse hypothalamus and basal forebrain during influenza infection: a novel model for sleep regulation

Ming Ding and Linda A. Toth

Department of Pharmacology, Southern Illinois University School of Medicine, Springfield, Illinois

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.

Temt; Ptgds; Lcn2; sinefungin; selenium; prostaglandin






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