Work completed under the current award established that infectious disease as a cause of increased somnolence, and supported the hypothesis that sleep enhancement during microbial infections is related to the immune response. However, the precise interactions between sleep, infection and immunity remain largely undetermined. The fundamental goal of the proposed experiments is to discover the mechanisms responsible for sleep enhancement during infectious disease. Specific cytokines and cell populations are hypothesized to mediate sleep enhancement during microbial infections. This hypothesis will be tested by studying sleep in mice infected with influenza virus. Preliminary data suggest that endogenous somnogenic cytokines such as interferon play a role in mediating virus-induced sleep potentiation in mice. For example a strain of mice (C57BL/s) which possesses genes for high interferon production after viral infection shows marked sleep enhancement during influenza infection, whereas a strain (BALB/c) which possesses genes for low production does not. The proposed experiments will study mice with specific genetic or immunologically-induced impairments in immune function to determine which cellular mechanisms and endogenous somnogenic cytokines are associated with sleep during influenza infection. A related study will characterize the effects of microbial somnogens and somnogenic cytokines on neuronal firing patterns in brain regions that regulate sleep. These experiments will use rats implanted with microwire electrodes that permit repeated chronic recording from individual neurons.

Agency
National Institute of Health (NIH)
Institute
National Institute of Neurological Disorders and Stroke (NINDS)
Type
Research Project (R01)
Project #
2R01NS026429-07A2
Application #
2265930
Study Section
Special Emphasis Panel (ZRG1-BPO (02))
Project Start
1989-04-01
Project End
1999-05-31
Budget Start
1995-08-01
Budget End
1996-05-31
Support Year
7
Fiscal Year
1995
Total Cost
Indirect Cost
Name
St. Jude Children's Research Hospital
Department
Type
DUNS #
067717892
City
Memphis
State
TN
Country
United States
Zip Code
38105
Trammell, Rita A; Brooks, Marjory; Cox, Lisa et al. (2006) Fatal hemorrhagic diathesis associated with mild factor IX deficiency in pl/J mice. Comp Med 56:426-34
Toth, Linda A; Hughes, Larry F (2006) Sleep and temperature responses of inbred mice with Candida albicans-induced pyelonephritis. Comp Med 56:252-61
Toth, Linda A; Hughes, Larry F (2004) Macrophage participation in influenza-induced sleep enhancement in C57BL/6J mice. Brain Behav Immun 18:375-89
Toth, L A; Verhulst, S J (2003) Strain differences in sleep patterns of healthy and influenza-infected inbred mice. Behav Genet 33:325-36
Toth, L A (2001) Identifying genetic influences on sleep: an approach to discovering the mechanisms of sleep regulation. Behav Genet 31:39-46
Toth, L A; Opp, M R (2001) Cytokine- and microbially induced sleep responses of interleukin-10 deficient mice. Am J Physiol Regul Integr Comp Physiol 280:R1806-14
Hayes, K E; Raucci Jr, J A; Gades, N M et al. (2000) An evaluation of analgesic regimens for abdominal surgery in mice. Contemp Top Lab Anim Sci 39:18-23
Toth, L A (2000) Defining the moribund condition as an experimental endpoint for animal research. ILAR J 41:72-9
Taylor, R; Hayes, K E; Toth, L A (2000) Evaluation of an anesthetic regimen for retroorbital blood collection from mice. Contemp Top Lab Anim Sci 39:14-7
Xi, X; Toth, L A (2000) Lipopolysaccharide effects on neuronal activity in rat basal forebrain and hypothalamus during sleep and waking. Am J Physiol Regul Integr Comp Physiol 278:R620-7

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