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Please use this identifier to cite or link to this item: http://hdl.handle.net/2262/62415

Title: Pharmacological inhibition of endocannabinoid degradation modulates the expression of inflammatory mediators in the hypothalamus following an immunological stressor
Author: CONNOR, THOMAS JOSEPH
Sponsor: Science Foundation Ireland
Author's Homepage: http://people.tcd.ie/connort
Keywords: Neuroscience
Immunology
Endocannabinoid
anandamide
Issue Date: 2012
Citation: D.M. Kerr, N.N. Burke, G.K. Ford, T.J. Connor, B. Harhen, L.J. Egan, D.P. Finn, M. Roche, Pharmacological inhibition of endocannabinoid degradation modulates the expression of inflammatory mediators in the hypothalamus following an immunological stressor, Neuroscience, 204, 2012, 53 - 63
Series/Report no.: Neuroscience;
204;
Abstract: 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 of URB597, a selective inhibitor of fatty acid amine hydrolyase (FAAH), the enzyme that preferentially metabolises 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 -palmitoyl ethanolamide and N-oleoyl ethanolamide, but not 2-arachidonoyl glycerol, in the hypothalamus and spleen. URB597 attenuated the LPS-induced increase in interleukin (IL)-1β 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.
Description: PUBLISHED
URI: http://hdl.handle.net/2262/62415
Related links: http://dx.doi.org/10.1016/j.neuroscience.2011.09.032
Appears in Collections:Physiology (Scholarly Publications)

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