Tumor necrosis factor (TNF) ligand and TNF receptor deficiency affects sleep and the sleep EEG.
Tumor necrosis factor (TNF) and lymphotoxin-alpha (LT-alpha) are proinflammatory cytokines involved in host defense and pathogenesis of various diseases. In addition, there is evidence that TNF is involved in sleep. TNF and LT-alpha both bind to the tumor necrosis factor receptors (TNFR). Recently, it was shown that TNF receptor 1 (TNFR1) knockout mice (R1KO) sleep less during the light period than controls. We investigated the effect of a TNF and LT-alpha double deficiency on sleep in mice (Ligand KO) and compared their sleep with that of R1KO, TNFR2 knockout (R2KO) mice, and wild-type (WT) controls. All mice were adapted to a 12:12 h light:dark cycle and their electroencephalographs (EEG) and electromyographs (EMG) were continuously recorded during a baseline day, 6-h sleep deprivation (SD), and 18-h recovery. Ligand KO and R2KO had 15% less rapid eye movement (REM) sleep during the baseline light period due to a reduction in REM sleep episode frequency. After SD, all genotypes showed an initial increase in slow-wave activity (SWA) (EEG power density between 0.75 and 4.0 Hz) in non-REM sleep, which gradually declined in the following hours. In Ligand KO the increase was mainly caused by an increase in fast SWA (2.75-4.0 Hz), which was also increased in R2KO. In contrast, in R1KO mice the increase was limited to the slow portion of SWA (0.75-2.5 Hz). R2KO and WT mice showed increases in both frequency ranges. The sub-division into fast and slow SWA frequencies corresponds to previous electrophysiological data where the two types of slow-waves were induced by either excitatory or inhibitory stimuli. Our data suggest that in Ligand KO the SWA increase is caused by an increase in excitatory input to the cortex, whereas in R1KO this input seems to be almost absent.
Deboer
Tom
T
Institute of Pharmacology and Toxicology, CH-8057, Switzerland. Tom.de_Boer@lumc.nl
Fontana
Adriano
A
Tobler
Irene
I
D000818:Animals; D004569:Electroencephalography; D004576:Electromyography; D008233:Lymphotoxin-alpha / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D018124:Receptors, Tumor Necrosis Factor / Q000172:deficiency / Q000502:physiology*; D012890:Sleep / Q000502:physiology*; D012894:Sleep Stages; D014409:Tumor Necrosis Factor-alpha / Q000172:deficiency / Q000502:physiology*
D008233:Lymphotoxin-alpha; D018124:Receptors, Tumor Necrosis Factor; D014409:Tumor Necrosis Factor-alpha