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J Appl Physiol 95: 460-468, 2003. First published February 21, 2003; doi:10.1152/japplphysiol.01190.2002
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Alterations in EEG activity and sleep after influenza viral infection in GHRH receptor-deficient mice

Jeremy A. Alt,1 Ferenc Obal, Jr.,2 T. R. Traynor,1 Janos Gardi,3 Jeannine A. Majde,1 and James M. Krueger1

1Department of Veterinary and Comparative Anatomy, Pharmacology and Physiology, Washington State University, Pullman, Washington 99164-6520; and 2Department of Physiology and 3Endocrine Unit, University of Szeged, A. Szent-Györgyi Medical Center, 6720 Szeged, Hungary

Submitted 23 December 2002 ; accepted in final form 17 February 2003

Viral infections induce excess non-rapid eye movement sleep (NREMS) in mice. Growth hormone-releasing hormone receptor (GHRH receptor) was previously identified as a candidate gene responsible for NREMS responses to influenza challenge in mice. The dwarf lit/lit mouse with a nonfunctional GHRH receptor was used to assess the role of the GHRH receptor in viral-induced NREMS. After influenza A virus infection the duration and intensity [electroencephalogram (EEG) delta power] of NREMS increased in heterozygous mice with the normal phenotype, whereas NREMS and EEG delta power decreased in homozygous lit/lit mice. Lit/lit mice developed a pathological state with EEG slow waves and enhanced muscle tone. Other influenza-induced responses (decreases in rapid eye movement sleep, changes in the EEG high-frequency bands during the various stages of vigilance, hypothermia, and decreased motor activity) did not differ between the heterozygous and lit/lit mice. GH replacement failed to normalize the NREMS responses in the lit/lit mice after influenza inoculation. Decreases in NREMS paralleled hypothermia in the lit/lit mice. Lung virus levels were similar in the two mouse strains. Lit/lit mice had a higher death rate after influenza challenge than the heterozygotes. In conclusion, GHRH signaling is involved in the NREMS response to influenza infection.

growth hormone-releasing hormone receptor; growth hormone; fever; non-rapid eye movement sleep; rapid eye movement sleep; lit/lit mice; electroencephalogram



Address for reprint requests and other correspondence: J. M. Krueger, Washington State Univ., College of Veterinary Medicine, Dept. of VCAPP, PO Box 646520, Pullman, WA 99164-6520 (E-mail: krueger{at}vetmed.wsu.edu).




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