Suplemento 2 Vol 8 No 1.indd - Universidad Veracruzana

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Revista Médica
LA FUNCIÓN BIOLÓGICA DEL SUEÑO
Humoral Regulation of Sleep; Implications for Sleep as an
Emergent Use-Dependent Local Process
James M. Krueger
Sleep and Performance Research Center
Program in Neuroscience
Washington State University
Krueger JM.
Humoral Regulation of Sleep; Implications for Sleep as an Emergent Use-Dependent Local Process
Rev Med UV 2008; Sup 2 8(1): 46-52.
ABSTRACT
Sleep is regulated in part by substances that are produced in
response to wakefulness cellular activity. These substances in turn
induce state changes in neural networks. Several of these sleep
regulatory substances are well-characterized and include tumor
necrosis factor (TNF), interleukin-1, adenosine, prostaglandin D , 2
and growth hormone releasing hormone. This review is focused on
TNF -sleep mechanisms. ATP co-released during neurotransmission
induces the release of TNF from glia via purine P2 receptors. TNF
acts directly on neurons to alter membrane potentials and gene
expression of adenosine and glutamate receptors. Changes in the
number of these receptors on neurons alter the sensitivities of
the neurons. Thus the input-output relationships of the networks
within which the neurons are located are changed. We posit that
these events lead to state oscillations and these changes are thus
use-dependent and local. The concept that cortical assemblies
such as cortical columns oscillate between states has broad
implications for sleep regulation, pathologies and function.
Sleep deprivation is associated with enhanced sleepiness,
sleep, and fatigue, increased sensitivity to pain and to
kindling stimuli, reduced memory and cognitive function,
and performance impairments. Chronic sleep loss is also
associated with pathologies such as metabolic syndrome,
chronic inflammation and cardiovascular disease. Multiple
disease states are characterized by increases in sleep,
sleepiness and fatigue including; sleep apnea, insomnia,
excessive daytime sleepiness, AIDS, myocardial infarction,
pre-eclampsia, post-dialysis fatigue, alcoholism, chronic
fatigue syndrome, post-viral fatigue syndrome, rheumatoid
arthritis and influenza viral infection. These disease states
and sleep loss are all associated with enhanced circulating
levels of cytokines such as tumor necrosis factor alpha
(TNF) and interleukin-1 (IL1) 1 . There is also animal
literature implicating these cytokines in physiological
sleep regulation and in the sleep responses occurring after
Revista Médica de la Universidad Veracruzana / Suplemento 2 Vol. 8 núm. 1, Enero - Junio 2008