Cited by 446Cannabis and Cannabinoid ResearchNeuroinflammation and Neurodegeneration MechanismsPain Mechanisms and Treatments

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The Endocannabinoid Anandamide Protects Neurons during CNS Inflammation by Induction of MKP-1 in Microglial Cells

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Eljaschewitsch, Eva, Witting, Anke, Mawrin, Christian, Lee, Thomas, Schmidt, Peter M., Wolf, Susanne, Hoertnagl, Heide, Raine, Cedric S., Schneider-Stock, Regine, Nitsch, Robert, Ullrich, Oliver·2006·Neuron

DOI 10.1016/j.neuron.2005.11.027

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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.

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Authors: Eljaschewitsch, E., Witting, A., Mawrin, C., Lee, T., Schmidt, P. M., Wolf, S., Hoertnagl, H., Raine, C. S., Schneider-Stock, R., Nitsch, R., & Ullrich, O.
Affiliations: Otto-von-Guericke-Universität Magdeburg (DE)
University of Washington (US)
Charité – Universitätsmedizin Berlin (DE)
Max Delbrück Center (DE)
Albert Einstein College of Medicine (US)
Corresponding author: Ullrich, Oliver
ORCID: Mawrin, Christian
Schmidt, Peter M.
Wolf, Susanne
Raine, Cedric S.
Nitsch, Robert
Ullrich, Oliver
Venue: Neuron
Publisher: Elsevier BV
Published: 2006-01
Volume: 49
Issue: 1
Pages: 67-79
ISSN: 0896-6273 (ISSN-L)
DOI: 10.1016/j.neuron.2005.11.027
OpenAlex: W1968740815
Cited by: 445
References: 76
Citations by year: 2026: 11 · 2025: 17 · 2024: 12 · 2023: 14 · 2022: 26 · 2021: 17 · 2020: 10 · 2019: 16 · 2018: 13 · 2017: 18 · 2016: 25 · 2015: 29 · 2014: 23 · 2013: 20 · 2012: 31
FWCI: 23.59
Type: journal article
Language: en
Open access: bronze
doi.org
Licence: www.elsevier.com/tdm/userlicense/1.0/ (tdm)
www.elsevier.com/open-access/userlicense/1.0/ (vor, 2754 d)
Locations: Neuron (publishedVersion)
PubMed (publishedVersion)
MDC Repository (Max-Delbrueck-Center for Molecular Medicine) (submittedVersion)
Funders: University of Miami
Deutsche Forschungsgemeinschaft
National Institutes of Health
National Heart, Lung, and Blood Institute (N01-HO-3284)
National Institute of Mental Health (R24-MH-59724, R24MH059724)
National Institute of Neurological Disorders and Stroke (NS-08952, NS-11920, R01NS008952)
Topics: Health Sciences › Medicine › Pharmacology (medical) › Cannabis and Cannabinoid Research
Life Sciences › Neuroscience › Neurology › Neuroinflammation and Neurodegeneration Mechanisms
Health Sciences › Medicine › Physiology (medical) › Pain Mechanisms and Treatments
Keywords: anandamide, endocannabinoid system, MKP-1, microglia, neuroinflammation, neuroprotection, CB1 receptor, CB2 receptor, MAPK signaling, histone H3 phosphorylation, neuroimmune interactions, pattern recognition receptors, excitotoxicity, secondary neuronal damage
MeSH terms: Adult, Animals, Arachidonic Acids, Cell Survival, Cells, Cultured, Encephalitis, Humans, Middle Aged, Multiple Sclerosis, Neurons, Nitric Oxide, Phosphoprotein Phosphatases, Phosphorylation, Tissue Distribution, Protein Tyrosine Phosphatases, Rats, Wistar, Microglia, Immediate-Early Proteins, Neuroprotective Agents, Cell Cycle Proteins, Nitric Oxide Synthase, MAP Kinase Signaling System, Receptors, Cannabinoid, Extracellular Signal-Regulated MAP Kinases, Mice, Rats, Polyunsaturated Alkamides, Dual Specificity Phosphatase 1, Protein Phosphatase 1, Cannabinoid Receptor Modulators, Endocannabinoids

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The Endocannabinoid Anandamide Protects Neurons during CNS Inflammation by Induction of MKP-1 in Microglial Cells

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