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Publication : The role of nitric oxide synthases in the sleep responses to tumor necrosis factor-alpha.

First Author  Chen L Year  2004
Journal  Brain Behav Immun Volume  18
Issue  4 Pages  390-8
PubMed ID  15157956 Mgi Jnum  J:105452
Mgi Id  MGI:3615091 Doi  10.1016/j.bbi.2003.12.002
Citation  Chen L, et al. (2004) The role of nitric oxide synthases in the sleep responses to tumor necrosis factor-alpha. Brain Behav Immun 18(4):390-8
abstractText  It is well established that cytokines such as tumor necrosis factor-alpha (TNFalpha) and interleukin-1beta (IL-1beta) are involved in physiological sleep regulation, yet their downstream somnogenic mechanisms remain largely uninvestigated. Nitric oxide (NO) is an effector molecule for some TNFalpha actions. Neuronal nitric oxide synthase (nNOS) and inducible nitric oxide synthase (iNOS) gene knockout (KO) mice sleep differently than their respective controls. In this study, we tested the hypothesis that NO mediates TNFalpha-induced sleep using iNOS and nNOS KO mice and their corresponding wild-type controls. Systemic administration of TNFalpha increased non-rapid eye movement sleep (NREMS) in the two control strains and in the iNOS KO mice during the first 4 h post-injection but failed to increase NREMS in nNOS KO mice. Rapid eye movement sleep (REMS) was suppressed by TNFalpha in nNOS controls but not in the other strains examined. The results suggest that TNFalpha affects sleep, in part, through nNOS.
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