Kindling Stimuli Delivered at Different Times in the Sleep-Wake Cycle

Abstract

These observations argue that amygdala-kindling-induced sleep-wake alterations are modulated by central increases in CRH or IL-1.

The Role of Cytokines in Sleep Regulation

“…There is an extensive literature relating neuronal activity to neurotrophin expression [reviewed 67] and these relationships form in part the basis of the neurotrophin hypothesis [68]. Other cytokines such as IL1 are less well studied in this regard although it is known that excessive endogenous stimulation, as occurs during kindling [4] or during sleep deprivation [69], enhances IL1 expression. Activity in neurons is translated into pre-and post-synaptic events that manifest in both the short run and long run.…”

“…The evidence that cytokines are involved in physiological sleep regulation and their relationships to other sleep regulatory substances (SRSs) is the focus of this review [reviewed 1,2,3]. Many laboratories have developed what is now overwhelming evidence linking sleep deprivation-enhanced inter-leukin-1 beta (IL1), and the related cytokine tumor necrosis factor alpha (TNF), to symptoms associated with sleep deprivation, such as sensitivity to kindling [4] and pain stimuli [5,6,7], cognitive [8,9,10], memory [11,12,13], and performance impairments [11], depression [14,15], sleepiness [2,16,17], and fatigue [14,18,19]. Further, chronic sleep loss is associated with pathologies such as metabolic syndrome [20,21,22], chronic inflammation [23,24], and cardiovascular disease [reviewed 25].…”

Biochemical Regulation of Sleep and Sleep Biomarkers

“…IL1 and TNF are pleiotropic, serving both physiological and pathological functions including modulation of memory, mood, inflammation and sleep. Sleep loss and altered cytokine levels are associated with enhanced sensitivity to pain 12,13 and kindling stimuli, 14 fatigue, [15][16][17] sleepiness and rebound sleep, metabolic syndrome 18,19 including type-2 diabetes, 20 and impaired cognition 21,22 and memory. [23][24][25] These sleep loss-associated symptoms can be elicited by injections of TNF or IL1.…”

Biphasic effects of baicalin, an active constituent of Scutellaria baicalensis Georgi, in the spontaneous sleep–wake regulation

“…IL-1␤ administered centrally into rats during their active period (dark period) is particularly effective in increasing SWS and reducing waking (Opp and Krueger, 1992;Krueger and Fang, 1999). Besides their effects on physiological sleep regulation, proinflammatory cytokines, including IL-1␤ and TNF-␣, have previously depicted the implication of pathological sleep disruption caused by neurological diseases, such as epilepsy and Parkinson's disease (Yi et al, 2004(Yi et al, , 2007Lu et al, 2010). Because the expression of IL-1␤ is highest during the light period and baicalin possesses the ability to suppress IL-1's effect (as aforementioned), we speculated that the baicalin-induced SWS decrement during the first 2 h of the light period is due to the blockade of IL-1 receptors, the decrease of IL-1 production, or both.…”