Acute hypoxia activates the neuroimmune system, which diabetes exacerbates

Daniel R. Johnson, Jason O'connor, Matthew E. Hartman, Richard I. Tapping, Gregory G. Freund

Research output: Contribution to journalArticle

28 Citations (Scopus)

Abstract

Acute hypoxia is experienced in an array of ailments and conditions, including asthma, chronic obstructive pulmonary disease, heart failure, sleep apnea, acute hypotension, and blast lung injury. Classically, infection activates the neuroimmune system, causing loss of interest in the social environment. We report that the non-infectious stimulus acute hypoxia triggers neuroimmune system activation (NSA), causing loss of interest in the social environment, and that recovery from hypoxia-induced NSA is impaired in a mouse model of type 2 diabetes. Importantly, recovery from the behavioral consequences of hypoxia-induced NSA was nearly ablated in MyD88 (myeloid differentiation factor 88) knock-out mice and in mice intracerebroventricularly administered the caspase-1 inhibitor ac-YVAD-CMK (ac-Tyr-Val-Asp-2,6- dimethylbenzoyloxymethylketone). Diabetic mice had prolonged recovery from NSA that could be halved by administration of subcutaneous interleukin-1 (IL-1) receptor antagonist (RA). These results show that acute hypoxia activates the IL-1β arm of the neuroimmune system, which diabetes exacerbates and treatment with IL-1RA ameliorates.

Original languageEnglish (US)
Pages (from-to)1161-1166
Number of pages6
JournalJournal of Neuroscience
Volume27
Issue number5
DOIs
StatePublished - Jan 31 2007
Externally publishedYes

Fingerprint

Social Environment
Myeloid Differentiation Factor 88
Blast Injuries
Interleukin-1 Receptors
Sleep Apnea Syndromes
Lung Injury
Interleukin-1
Knockout Mice
Hypotension
Chronic Obstructive Pulmonary Disease
Type 2 Diabetes Mellitus
Asthma
Heart Failure
Hypoxia
Infection
interleukin-1beta-converting enzyme inhibitor
N-acetyl-tyrosyl-valyl-alanyl-aspartyl chloromethyl ketone

Keywords

  • Caspase-1
  • Hypoxia
  • IL-1 receptor antagonist
  • IL-1β
  • Innate immunity
  • Myeloid differentiation factor 88
  • Neuroimmunity
  • Type 2 diabetes

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Acute hypoxia activates the neuroimmune system, which diabetes exacerbates. / Johnson, Daniel R.; O'connor, Jason; Hartman, Matthew E.; Tapping, Richard I.; Freund, Gregory G.

In: Journal of Neuroscience, Vol. 27, No. 5, 31.01.2007, p. 1161-1166.

Research output: Contribution to journalArticle

Johnson, Daniel R. ; O'connor, Jason ; Hartman, Matthew E. ; Tapping, Richard I. ; Freund, Gregory G. / Acute hypoxia activates the neuroimmune system, which diabetes exacerbates. In: Journal of Neuroscience. 2007 ; Vol. 27, No. 5. pp. 1161-1166.
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