Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
1999-2-11
pubmed:abstractText
There is mounting evidence that inflammation and associated excitotoxicity may play important roles in various neurodegenerative disorders, such as bacterial infections, Alzheimer's disease, AIDS dementia, and multiple sclerosis. The immunogen E. coli lipopolysaccharide (LPS, endotoxin) has been widely used to stimulate immune/inflammatory responses both systemically and in the CNS. Here, we show that exposure of parietal cortical slices from adult rats to LPS triggered very rapid (<2.5 min) and sustained releases of the neurotransmitters glutamate and noradrenaline, and of the neuromodulator adenosine. The responses to LPS declined rapidly following removal of the LPS and exhibited no tachyphylaxis to repeated exposures to LPS. The detoxified form of LPS had no effect. LPS-evoked release of [3H]noradrenaline, but not of glutamate or adenosine, appears to be partly due to the released glutamate acting at ionotropic receptors on the noradrenergic axons present in the cortical slices. LPS appears to release glutamate, which then acts at non-NMDA receptors to remove the voltage-sensitive Mg2+ block of NMDA receptors, thus permitting NMDA receptors to be activated and noradrenaline release to proceed. It seems possible that rapid, inappropriate excitation may occur in the immediate vicinity of gram-negative bacterial infections in the brain. If similar inappropriate excitations are also triggered by those immunogens specifically associated with Alzheimer's disease (beta-amyloid), AIDS dementia (gp120 and gp41), or multiple sclerosis (myelin basic protein), they might explain some of the acute, transient neurological and psychiatric symptoms associated with these disorders.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
http://linkedlifedata.com/resource/pubmed/chemical/2,3-dioxo-6-nitro-7-sulfamoylbenzo(f..., http://linkedlifedata.com/resource/pubmed/chemical/Adenosine, http://linkedlifedata.com/resource/pubmed/chemical/Dizocilpine Maleate, http://linkedlifedata.com/resource/pubmed/chemical/Excitatory Amino Acid Antagonists, http://linkedlifedata.com/resource/pubmed/chemical/Glutamic Acid, http://linkedlifedata.com/resource/pubmed/chemical/Lipopolysaccharides, http://linkedlifedata.com/resource/pubmed/chemical/Neuroprotective Agents, http://linkedlifedata.com/resource/pubmed/chemical/Norepinephrine, http://linkedlifedata.com/resource/pubmed/chemical/Quinoxalines, http://linkedlifedata.com/resource/pubmed/chemical/Receptors, N-Methyl-D-Aspartate, http://linkedlifedata.com/resource/pubmed/chemical/Sympathomimetics, http://linkedlifedata.com/resource/pubmed/chemical/Tritium
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
72
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
652-60
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:9930737-Adenosine, pubmed-meshheading:9930737-Age Factors, pubmed-meshheading:9930737-Animals, pubmed-meshheading:9930737-Cerebral Cortex, pubmed-meshheading:9930737-Dizocilpine Maleate, pubmed-meshheading:9930737-Excitatory Amino Acid Antagonists, pubmed-meshheading:9930737-Glutamic Acid, pubmed-meshheading:9930737-Lipopolysaccharides, pubmed-meshheading:9930737-Male, pubmed-meshheading:9930737-Neuroprotective Agents, pubmed-meshheading:9930737-Norepinephrine, pubmed-meshheading:9930737-Organ Culture Techniques, pubmed-meshheading:9930737-Parietal Lobe, pubmed-meshheading:9930737-Quinoxalines, pubmed-meshheading:9930737-Rats, pubmed-meshheading:9930737-Rats, Sprague-Dawley, pubmed-meshheading:9930737-Receptors, N-Methyl-D-Aspartate, pubmed-meshheading:9930737-Sympathomimetics, pubmed-meshheading:9930737-Tritium
pubmed:year
1999
pubmed:articleTitle
The bacterial endotoxin lipopolysaccharide causes rapid inappropriate excitation in rat cortex.
pubmed:affiliation
Department of Pharmacology, Dalhousie University, Halifax, Nova Scotia, Canada.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't