|
rdf:type |
|
|
lifeskim:mentions |
|
|
pubmed:issue |
6
|
|
pubmed:dateCreated |
2005-3-7
|
|
pubmed:abstractText |
Theiler's virus infection of the central nervous system (CNS) induces an immune-mediated demyelinating disease in susceptible mouse strains and serves as a relevant infection model for human multiple sclerosis (MS). Cannabinoids have been shown to exert beneficial effects on animal models of MS and evidence suggests that the endocannabinoid system plays a role in the tonic control of spasticity. In this study we show that OMDM1 [(R)-N-oleoyl-(1'-hydroxybenzyl)-2'-ethanolamine] and OMDM2 [(S)-N-oleoyl-(1'-hydroxybenzyl)-2'-ethanolamine], two selective inhibitors of the putative endocannabinoid transporter and hence of endocannabinoid inactivation, provide an effective therapy for Theiler murine encephalomyelitis virus-induced demyelinating disease (TMEV-IDD). Treatment of TMEV-infected mice with OMDM1 and OMDM2 enhanced anandamide levels in the spinal cord and ameliorated motor symptoms. This was associated with a down-regulation of inflammatory responses in the spinal cord. In addition we show that OMDM1 and OMDM2 down-regulate macrophage function by (i) decreasing the surface expression of major histocompatibility complex (MHC) class II molecules, (ii) inhibiting nitric oxide synthase-2 (NOS-2) expression and (iii) reducing the production of the pro-inflammatory cytokines interleukin-1beta (IL-1beta) and interleukin-12 (IL-12p40). Taken together, these results point to the manipulation of the endocannabinoid system as a possible strategy to develop future MS therapeutic drugs.
|
|
pubmed:language |
eng
|
|
pubmed:journal |
|
|
pubmed:citationSubset |
IM
|
|
pubmed:chemical |
http://linkedlifedata.com/resource/pubmed/chemical/Arachidonic Acids,
http://linkedlifedata.com/resource/pubmed/chemical/Benzyl Compounds,
http://linkedlifedata.com/resource/pubmed/chemical/Carrier Proteins,
http://linkedlifedata.com/resource/pubmed/chemical/Cytokines,
http://linkedlifedata.com/resource/pubmed/chemical/Endocannabinoids,
http://linkedlifedata.com/resource/pubmed/chemical/Histocompatibility Antigens Class II,
http://linkedlifedata.com/resource/pubmed/chemical/Inflammation Mediators,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase,
http://linkedlifedata.com/resource/pubmed/chemical/Nitric Oxide Synthase Type II,
http://linkedlifedata.com/resource/pubmed/chemical/Nos2 protein, mouse,
http://linkedlifedata.com/resource/pubmed/chemical/OMDM-1 cpd,
http://linkedlifedata.com/resource/pubmed/chemical/OMDM-2 cpd,
http://linkedlifedata.com/resource/pubmed/chemical/Polyunsaturated Alkamides,
http://linkedlifedata.com/resource/pubmed/chemical/anandamide
|
|
pubmed:status |
MEDLINE
|
|
pubmed:month |
Mar
|
|
pubmed:issn |
0022-3042
|
|
pubmed:author |
|
|
pubmed:issnType |
Print
|
|
pubmed:volume |
92
|
|
pubmed:owner |
NLM
|
|
pubmed:authorsComplete |
Y
|
|
pubmed:pagination |
1327-39
|
|
pubmed:dateRevised |
2006-11-15
|
|
pubmed:meshHeading |
pubmed-meshheading:15748152-Animals,
pubmed-meshheading:15748152-Arachidonic Acids,
pubmed-meshheading:15748152-Benzyl Compounds,
pubmed-meshheading:15748152-Cardiovirus Infections,
pubmed-meshheading:15748152-Carrier Proteins,
pubmed-meshheading:15748152-Cytokines,
pubmed-meshheading:15748152-Disease Models, Animal,
pubmed-meshheading:15748152-Endocannabinoids,
pubmed-meshheading:15748152-Female,
pubmed-meshheading:15748152-Histocompatibility Antigens Class II,
pubmed-meshheading:15748152-Inflammation,
pubmed-meshheading:15748152-Inflammation Mediators,
pubmed-meshheading:15748152-Macrophages,
pubmed-meshheading:15748152-Mice,
pubmed-meshheading:15748152-Microglia,
pubmed-meshheading:15748152-Motor Activity,
pubmed-meshheading:15748152-Multiple Sclerosis,
pubmed-meshheading:15748152-Nitric Oxide Synthase,
pubmed-meshheading:15748152-Nitric Oxide Synthase Type II,
pubmed-meshheading:15748152-Polyunsaturated Alkamides,
pubmed-meshheading:15748152-Theilovirus,
pubmed-meshheading:15748152-Up-Regulation
|
|
pubmed:year |
2005
|
|
pubmed:articleTitle |
Pharmacological modulation of the endocannabinoid system in a viral model of multiple sclerosis.
|
|
pubmed:affiliation |
Neuroimmunology Group, Neural Plasticity Department, Cajal Institute, CSIC, 28002 Madrid, Spain.
|
|
pubmed:publicationType |
Journal Article,
Research Support, Non-U.S. Gov't
|
