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rdf:type |
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lifeskim:mentions |
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pubmed:issue |
2
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pubmed:dateCreated |
2010-1-28
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pubmed:abstractText |
After injury or during neurodegenerative disease in the central nervous system (CNS), the concentration of tumor necrosis factor alpha (TNFalpha) rises above normal during the inflammatory response. In vitro and in vivo, addition of exogenous TNFalpha to neurons has been shown to induce rapid plasma membrane-delivery of AMPA-type glutamate receptors (AMPARs) potentiating glutamatergic excitotoxicity. Thus the discovery of drug targets reducing excess TNFalpha-induced AMPAR surface expression may help protect neurons after injury. In this study, we investigate the neuroprotective role of the CB1 cannabinoid receptor using quantitative immunofluorescent and real-time video microscopy to measure the steady-state plasma membrane AMPAR distribution and rate of AMPAR exocytosis after TNFalpha exposure in the presence or absence of CB1 agonists. The neuroprotective potential of CB1 activation with TNFalpha was measured in hippocampal neuron cultures challenged by an in vitro kainate (KA)-mediated model of Excitotoxic Neuroinflammatory Death (END). Here, we demonstrate that CB1 activation blocks the TNFalpha-induced increase in surface AMPARs and protects neurons from END. Thus, neuroprotective strategies which increase CB1 activity may help to reduce the END that occurs as a result of a majority of CNS insults.
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pubmed:grant |
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pubmed:language |
eng
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pubmed:journal |
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pubmed:citationSubset |
IM
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pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Benzoxazines,
http://linkedlifedata.com/resource/pubmed/chemical/Kainic Acid,
http://linkedlifedata.com/resource/pubmed/chemical/Morpholines,
http://linkedlifedata.com/resource/pubmed/chemical/Naphthalenes,
http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents,
http://linkedlifedata.com/resource/pubmed/chemical/Neurotoxins,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cannabinoid, CB1,
http://linkedlifedata.com/resource/pubmed/chemical/Receptor, Cannabinoid, CB2,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, AMPA,
http://linkedlifedata.com/resource/pubmed/chemical/Receptors, Cannabinoid,
http://linkedlifedata.com/resource/pubmed/chemical/Tumor Necrosis Factor-alpha,
http://linkedlifedata.com/resource/pubmed/chemical/Win 55212-2
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pubmed:status |
MEDLINE
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pubmed:month |
Feb
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pubmed:issn |
1873-7064
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pubmed:author |
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pubmed:copyrightInfo |
2009 Elsevier Ltd. All rights reserved.
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pubmed:issnType |
Electronic
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pubmed:volume |
58
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pubmed:owner |
NLM
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pubmed:authorsComplete |
Y
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pubmed:pagination |
551-8
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pubmed:dateRevised |
2011-4-11
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pubmed:meshHeading |
pubmed-meshheading:19654014-Animals,
pubmed-meshheading:19654014-Benzoxazines,
pubmed-meshheading:19654014-Cell Death,
pubmed-meshheading:19654014-Cell Membrane,
pubmed-meshheading:19654014-Cells, Cultured,
pubmed-meshheading:19654014-Exocytosis,
pubmed-meshheading:19654014-Hippocampus,
pubmed-meshheading:19654014-Kainic Acid,
pubmed-meshheading:19654014-Morpholines,
pubmed-meshheading:19654014-Naphthalenes,
pubmed-meshheading:19654014-Neurons,
pubmed-meshheading:19654014-Neuroprotective Agents,
pubmed-meshheading:19654014-Neurotoxins,
pubmed-meshheading:19654014-Rats,
pubmed-meshheading:19654014-Rats, Sprague-Dawley,
pubmed-meshheading:19654014-Receptor, Cannabinoid, CB1,
pubmed-meshheading:19654014-Receptor, Cannabinoid, CB2,
pubmed-meshheading:19654014-Receptors, AMPA,
pubmed-meshheading:19654014-Receptors, Cannabinoid,
pubmed-meshheading:19654014-Time Factors,
pubmed-meshheading:19654014-Tumor Necrosis Factor-alpha,
pubmed-meshheading:19654014-Video Recording
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pubmed:year |
2010
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pubmed:articleTitle |
Cannabinoid receptor activation reduces TNFalpha-induced surface localization of AMPAR-type glutamate receptors and excitotoxicity.
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pubmed:affiliation |
Forbes Norris ALS/MDA Research Center, California Pacific Medical Center Research Institute, 475 Brannan St., Suite 220, San Francisco, CA 94107, USA.
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pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't,
Research Support, N.I.H., Extramural
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