Extraction of sleep-promoting factor S from cerebrospinal fluid and from brains of sleep-deprived animals

Abstract

Sleep-promoting factor (factor S) was extracted, partially purified, and concentrated from cerebrospinal fluid and from acid-acetone extracts of brain stem anc cortex of sleep-deprived goats and sheep. 2. Solutes greater than 500 daltons were largely removed by serial ultrafiltrations through molecular sieves (Amicon membranes UM10 and UM05); solutes less than 350 daltons were largely eliminated by gel filtration through Sephadex G10 columns. Sleep-promoting activity was found in a fraction eluted prior to [14C] sucrose marker. 3. Concentrated fraction were infused intraventricularly in rats (0.1 ml in 30 min just prior to 12-h dark cycle) and in rabbits (0.3 ml in 90 min in morning). Sleep-promoting activity was assayed by decrease in nocturnal locomotor activity of rats and by duration and amplitude of slow-wave cortical EEG in rabbits.

TNFα siRNA reduces brain TNF and EEG delta wave activity in rats

“…Similar conclusions were reached previously after the demonstration that injection of TNFα onto the SSctx enhanced EEG SWA regionally whereas injection of the TNF soluble receptor reduced EEG SWA that had been enhanced by sleep loss (Yoshida et al, 2004). EEG SWA is posited to be indicative of sleep intensity (Borbely and Tobler 1989) because it is enhanced during the deep sleep following sleep deprivation (Pappenheimer et al, 1975). Microinjection of TNFα onto the surface of the SSctx also increases the amplitude of surface evoked potentials induced by whisker stimulation (Churchill et al, 2005a) in a fashion similar to the increase in surfaceevoked potentials during quiet sleep (Rector et al 2005), suggesting that increases in extracellular TNF can alter the physiological responses to neural stimulation.…”

Biochemical Regulation of Sleep and Sleep Biomarkers

“…[26][27][28][29] In addition to increasing time spent sleeping, these cytokines after central injection can enhance electroencephalographic (EEG) δ power (a measure of sleep intensity) during NREMS. This effect is similar to that seen after sleep deprivation 30 suggesting that IL1 and TNF injection mimics the effect of sleep loss.…”

Mice Lacking the TNF 55 kDa Receptor Fail to Sleep More After TNFα Treatment

“…In rats (Tobler et al, 1984;Opp et al, 1991) and rabbits (Krueger et al, 1984) these cytokines induce increases in EEG slow-wave activity after intracerebroventricular injections. Furthermore, during N REMS after sleep deprivation EEG slow-wave activity increases (Pappenheimer et al, 1975); this latter result is interpreted to indicate that EEG slow-wave activity is a measure of sleep intensity (Borbély and Tobler, 1989). Current results could be attributable to the route of administration.…”