Alterations in EEG activity and sleep after influenza viral infection in GHRH receptor-deficient mice.
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.
Alt
Jeremy A
JA
Department of Veterinary and Comparative Anatomy and Pphysiology, Washington State University, College of Veterinary Medicine, Pullman, WA 99164-6520, USA.
Obal
Ferenc
F
Traynor
T R
TR
Gardi
Janos
J
Majde
Jeannine A
JA
Krueger
James M
JM
D000818:Animals; D001831:Body Temperature; D001921:Brain / Q000821:virology; D004392:Dwarfism / Q000235:genetics / Q000378:metabolism; D004569:Electroencephalography; D013006:Growth Hormone / Q000008:administration & dosage; D006579:Heterozygote; D006720:Homozygote; D009980:Influenza A virus / Q000302:isolation & purification; D007260:Infusion Pumps; D007334:Insulin-Like Growth Factor I / Q000378:metabolism; D008168:Lung / Q000473:pathology / Q000821:virology; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D009976:Orthomyxoviridae Infections / Q000401:mortality / Q000473:pathology / Q000503:physiopathology* / Q000821:virology; D017354:Point Mutation; D018013:Receptors, Neuropeptide / Q000172:deficiency* / Q000235:genetics; D018017:Receptors, Pituitary Hormone-Regulating Hormone / Q000172:deficiency* / Q000235:genetics; D012890:Sleep / Q000187:drug effects; D012895:Sleep, REM; D019562:Viral Load
D018013:Receptors, Neuropeptide; D018017:Receptors, Pituitary Hormone-Regulating Hormone; D007334:Insulin-Like Growth Factor I; D013006:Growth Hormone; C048250:somatotropin releasing hormone receptor