Inflammation-sleep interface in brain disease: TNF, insulin, orexin

Clark, IA; Vissel, B

Inflammation-sleep interface in brain disease: TNF, insulin, orexin

Clark, IA Vissel, B

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Publication Type:: Journal Article
Citation:: Journal of Neuroinflammation, 2014, 11
Issue Date:: 2014-03-21

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Field	Value	Language
dc.contributor.author	Clark, IA	en_US
dc.contributor.author	Vissel, B https://orcid.org/0000-0001-8860-8050	en_US
dc.date.available	2014-03-11	en_US
dc.date.issued	2014-03-21	en_US
dc.identifier.citation	Journal of Neuroinflammation, 2014, 11	en_US
dc.identifier.uri	http://hdl.handle.net/10453/116585
dc.description.abstract	The depth, pattern, timing and duration of unconsciousness, including sleep, vary greatly in inflammatory disease, and are regarded as reliable indicators of disease severity. Similarly, these indicators are applicable to the encephalopathies of sepsis, malaria, and trypanosomiasis, and to viral diseases such as influenza and AIDS. They are also applicable to sterile neuroinflammatory states, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke and type-2 diabetes, as well as in iatrogenic brain states following brain irradiation and chemotherapy. Here we make the case that the cycles of unconsciousness that constitute normal sleep, as well as its aberrations, which range from sickness behavior through daytime sleepiness to the coma of inflammatory disease states, have common origins that involve increased inflammatory cytokines and consequent insulin resistance and loss of appetite due to reduction in orexigenic activity. Orexin reduction has broad implications, which are as yet little appreciated in the chronic inflammatory conditions listed, whether they be infectious or sterile in origin. Not only is reduction in orexin levels characterized by loss of appetite, it is associated with inappropriate and excessive sleep and, when dramatic and chronic, leads to coma. Moreover, such reduction is associated with impaired cognition and a reduction in motor control. We propose that advanced understanding and appreciation of the importance of orexin as a key regulator of pathways involved in the maintenance of normal appetite, sleep patterns, cognition, and motor control may afford novel treatment opportunities. © 2014 Clark and Vissel; licensee BioMed Central Ltd.	en_US
dc.relation.ispartof	Journal of Neuroinflammation	en_US
dc.relation.isbasedon	10.1186/1742-2094-11-51	en_US
dc.subject.classification	Neurology & Neurosurgery	en_US
dc.subject.mesh	Animals	en_US
dc.subject.mesh	Humans	en_US
dc.subject.mesh	Brain Diseases	en_US
dc.subject.mesh	Sleep Disorders	en_US
dc.subject.mesh	Inflammation	en_US
dc.subject.mesh	Insulin	en_US
dc.subject.mesh	Tumor Necrosis Factor-alpha	en_US
dc.subject.mesh	Intracellular Signaling Peptides and Proteins	en_US
dc.subject.mesh	Neuropeptides	en_US
dc.subject.mesh	Orexins	en_US
dc.subject.mesh	Sleep Wake Disorders	en_US
dc.title	Inflammation-sleep interface in brain disease: TNF, insulin, orexin	en_US
dc.type	Journal Article
utslib.citation.volume	11	en_US
utslib.for	1103 Clinical Sciences	en_US
utslib.for	1107 Immunology	en_US
utslib.for	1109 Neurosciences	en_US
pubs.embargo.period	Not known	en_US
pubs.organisational-group	/University of Technology Sydney
pubs.organisational-group	/University of Technology Sydney/Faculty of Science
pubs.organisational-group	/University of Technology Sydney/Faculty of Science/School of Life Sciences
utslib.copyright.status	open_access
pubs.publication-status	Published	en_US
pubs.volume	11	en_US

Abstract:

The depth, pattern, timing and duration of unconsciousness, including sleep, vary greatly in inflammatory disease, and are regarded as reliable indicators of disease severity. Similarly, these indicators are applicable to the encephalopathies of sepsis, malaria, and trypanosomiasis, and to viral diseases such as influenza and AIDS. They are also applicable to sterile neuroinflammatory states, including Alzheimer's disease, Parkinson's disease, traumatic brain injury, stroke and type-2 diabetes, as well as in iatrogenic brain states following brain irradiation and chemotherapy. Here we make the case that the cycles of unconsciousness that constitute normal sleep, as well as its aberrations, which range from sickness behavior through daytime sleepiness to the coma of inflammatory disease states, have common origins that involve increased inflammatory cytokines and consequent insulin resistance and loss of appetite due to reduction in orexigenic activity. Orexin reduction has broad implications, which are as yet little appreciated in the chronic inflammatory conditions listed, whether they be infectious or sterile in origin. Not only is reduction in orexin levels characterized by loss of appetite, it is associated with inappropriate and excessive sleep and, when dramatic and chronic, leads to coma. Moreover, such reduction is associated with impaired cognition and a reduction in motor control. We propose that advanced understanding and appreciation of the importance of orexin as a key regulator of pathways involved in the maintenance of normal appetite, sleep patterns, cognition, and motor control may afford novel treatment opportunities. © 2014 Clark and Vissel; licensee BioMed Central Ltd.

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http://hdl.handle.net/10453/116585