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Kerr, DM,Burke, NN,Ford, GK,Connor, TJ,Harhen, B,Egan, LJ,Finn, DP,Roche, M
2012
March
PHARMACOLOGICAL INHIBITION OF ENDOCANNABINOID DEGRADATION MODULATES THE EXPRESSION OF INFLAMMATORY MEDIATORS IN THE HYPOTHALAMUS FOLLOWING AN IMMUNOLOGICAL STRESSOR
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1
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endocannabinoid anandamide 2-AG cytokine HPA axis ACID AMIDE HYDROLASE NF-KAPPA-B MESSENGER-RNA EXPRESSION PITUITARY-ADRENAL AXIS CENTRAL-NERVOUS-SYSTEM RAT MICROGLIAL CELLS CYTOKINE SIGNALING-3 CB2 RECEPTORS HPA AXIS CANNABINOID RECEPTORS
The endocannabinoid system is an important regulator of the nervous, neuroendocrine, and immune systems, thus representing a novel therapeutic target for stress-related neuroinflammatory and psychiatric disorders. However, there is a paucity of data relating to the effects of endocannabinoids on neuroinflammatory mediators following an immune stress/challenge in vivo. This study investigated the effects or URB597, a selective inhibitor of fatty acid amide hydrolyase (FAAH), the enzyme that preferentially metabolizes anandamide, on lipopolysaccharide (LPS)-induced increases in the expression of immune mediators in the hypothalamus. Systemic administration of URB597 increased the levels of anandamide and the related N-acylethanolamines, N-palmitoylethanolamide, and N-oleoylethanolamide, but not 2-arachidonoyl glycerol, in the hypothalamus and spleen. URB597 attenuated the LPS-induced increase in interleukin (IL)-1 beta expression while concurrently augmenting the LPS-induced increase in suppressor of cytokine signalling (SOCS)-3 expression. In addition, URB597 tended to enhance and reduce the LPS-induced increase in IL-6 and IL-10 mRNA expression, respectively. LPS-induced increases in peripheral cytokine levels or plasma corticosterone were not altered by URB597. The present study provides evidence for a role for FAAH in the regulation of LPS-induced expression of inflammatory mediators in the hypothalamus. Improved understanding of endocannabinoid-mediated regulation of neuroimmune function has fundamental physiological and potential therapeutic significance in the context of stress-related disorders.This article is part of a Special Issue entitled: Stress, Emotional Behavior and the Endocannabinoid System. (C) 2011 IBRO. Published by Elsevier Ltd. All rights reserved.
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DOI 10.1016/j.neuroscience.2011.09.032
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