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The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells

Item Type:Article
Title:The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in microglial cells
Creators Name:Eljaschewitsch, E. and Witting, A. and Mawrin, C. and Lee, T. and Schmidt, P.M. and Wolf, S. and Hoertnagl, H. and Raine, C.S. and Schneider-Stock, R. and Nitsch, R. and Ullrich, O.
Abstract:Endocannabinoids are released after brain injury and believed to attenuate neuronal damage by binding to CB 1 receptors and protecting against excitotoxicity. Such excitotoxic brain lesions initially result in primary destruction of brain parenchyma, which attracts macrophages and microglia. These inflammatory cells release toxic cytokines and free radicals, resulting in secondary neuronal damage. In this study, we show that the endocannabinoid system is highly activated during CNS inflammation and that the endocannabinoid anandamide (AEA) protects neurons from inflammatory damage by CB 1/2 receptor-mediated rapid induction of mitogen-activated protein kinase phosphatase-1 (MKP-1) in microglial cells associated with histone H3 phoshorylation of the mkp-1 gene sequence. As a result, AEA-induced rapid MKP-1 expression switches off MAPK signal transduction in microglial cells activated by stimulation of pattern recognition receptors. The release of AEA in injured CNS tissue might therefore represent a new mechanism of neuro-immune communication during CNS injury, which controls and limits immune response after primary CNS damage.
Keywords:Arachidonic Acids, Cannabinoid Receptor Modulators, Cannabinoid Receptors, Cell Cycle Proteins, Cell Survival, Cultured Cells, Dual Specificity Phosphatase 1, Encephalitis, Endocannabinoids, Extracellular Signal-Regulated MAP Kinases, Immediate-Early Proteins, MAP Kinase Signaling System, Microglia, Multiple Sclerosis, Neurons, Neuroprotective Agents, Nitric Oxide, Nitric Oxide Synthase, Phosphoprotein Phosphatases, Phosphorylation, Polyunsaturated Alkamides, Protein Phosphatase 1, Protein Tyrosine Phosphatases, Tissue Distribution, Wistar Rats, Animals, Mice, Rats
Source:Neuron
ISSN:0896-6273
Publisher:Cell Press (U.S.A.)
Volume:49
Number:1
Page Range:67-79
Date:5 January 2006
Official Publication:https://doi.org/10.1016/j.neuron.2005.11.027
PubMed:View item in PubMed

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