Linked Life Data

18279310

Source:http://linkedlifedata.com/resource/pubmed/id/18279310

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2008-2-18
pubmed:abstractText
Amyotrophic lateral sclerosis (ALS) is a fatal neurodegenerative disorder involving the selective loss of spinal cord motor neurons. Excitotoxicity mediated by glutamate has been implicated as a cause of this progressive degeneration. In this study we examined two types of receptors, the excitatory alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid-type glutamate receptors (AMPARs) and inhibitory cannabinoid receptor (CB1) with respect to their localization and total expression in spinal cord motor neurons. AMPAR and CB1 represent major excitatory and inhibitory transmission input, respectively, and their expression levels on the plasma membrane have direct relevance to the vulnerability of the motor neurons to glutamatergic excitotoxicity. We used quantitative immunofluorescence microscopy to comparatively measure the total cellular expression and the synaptic localization of specific subclasses of AMPARs [as determined by the presence of the subunits glutamate receptor 1 (GluR1) or glutamate receptor 2 (GluR2)] and CB1 in spinal cord motor neurons during disease progression in a G93ASOD1 mouse model of ALS. We found an increase in synaptic GluR1 and a decrease of synaptic and total GluR2 at early ages (6 weeks, prior to disease onset). Total CB1 receptor levels were decreased at 6 weeks old. We determined the gene expression of CB1, GluR1 and GluR2 using quantitative real-time reverse transcriptase-polymerase chain reaction. The decreased synaptic and total GluR2 and increased synaptic GluR1 levels may result in increased numbers of Ca2+-permeable AMPARs, thus contributing to neuronal death. Early alterations in CB1 expression may also predispose motor neurons to excitotoxicity. To our knowledge, this is the first demonstration of presymptomatic changes in trafficking of receptors that are in direct control of excitotoxicity and death in a mouse model of ALS.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
1460-9568
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
27
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
572-9
pubmed:dateRevised
2011-9-22
pubmed:meshHeading
pubmed-meshheading:18279310-Amyotrophic Lateral Sclerosis, pubmed-meshheading:18279310-Animals, pubmed-meshheading:18279310-Cell Death, pubmed-meshheading:18279310-Disease Models, Animal, pubmed-meshheading:18279310-Down-Regulation, pubmed-meshheading:18279310-Female, pubmed-meshheading:18279310-Glutamic Acid, pubmed-meshheading:18279310-Humans, pubmed-meshheading:18279310-Male, pubmed-meshheading:18279310-Mice, pubmed-meshheading:18279310-Mice, Transgenic, pubmed-meshheading:18279310-Motor Neurons, pubmed-meshheading:18279310-Nerve Degeneration, pubmed-meshheading:18279310-Neural Inhibition, pubmed-meshheading:18279310-Neurotoxins, pubmed-meshheading:18279310-Protein Transport, pubmed-meshheading:18279310-Receptor, Cannabinoid, CB1, pubmed-meshheading:18279310-Receptors, AMPA, pubmed-meshheading:18279310-Spinal Cord, pubmed-meshheading:18279310-Synaptic Transmission, pubmed-meshheading:18279310-Up-Regulation
pubmed:year
2008
pubmed:articleTitle
Altered presymptomatic AMPA and cannabinoid receptor trafficking in motor neurons of ALS model mice: implications for excitotoxicity.
pubmed:affiliation
Forbes Norris ALS/MDA Research Center, California Pacific Medical Center Research Institute, 475 Brannan St, Suite 220, San Francisco, CA 94107, USA.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural