Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2005-6-29
pubmed:abstractText
Abnormalities in oxidative processes, region-selective neuron loss, inflammation and diminished activity of thiamine-dependent enzymes characterize age-related neurodegenerative diseases. Thiamine deficiency (TD) models the selective neurodegeneration that accompanies mild impairment of oxidative metabolism. As in human neurodegenerative diseases, alterations in multiple cell types accompany the TD-induced neurodegeneration. The current studies demonstrate that CD40 and CD40 ligand (CD40L), two co-stimulatory immune molecules, are involved in TD-induced selective neuronal death. TD induced CD40 immunoreactivity in microglia and CD40L immunoreactivity in astrocytes. Both CD40-positive microglia and CD40L-positive astrocytes increased during the progressive TD-induced neuronal death. In early stages of TD, targeted deletion of CD40 diminished the number of CD40L-positive astrocytes and reduced neuronal death by 35%. The number of CD40L-positive astrocytes increased whenever the number of NeuN-positive neurons decreased. In early stages of TD, deletion of CD40L diminished CD40-positive microglia and reduced the neuronal death by 64%. In advanced phases of TD, neither CD40 nor CD40L deletion protected against neuronal death. The data show for the first time that TD induces expression of CD40 by the microglia and CD40L by astrocytes. The results indicate that CD40-CD40L interactions promote neuronal death in early stages of TD, but that at later phases the protective effects of the diminished CD40 or CD40L are over-ridden by other mechanisms.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Aug
pubmed:issn
0197-0186
pubmed:author
pubmed:issnType
Print
pubmed:volume
47
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
204-15
pubmed:dateRevised
2007-11-14
pubmed:meshHeading
pubmed-meshheading:15885854-Animals, pubmed-meshheading:15885854-Antigens, CD40, pubmed-meshheading:15885854-Astrocytes, pubmed-meshheading:15885854-CD40 Ligand, pubmed-meshheading:15885854-Cell Death, pubmed-meshheading:15885854-Disease Models, Animal, pubmed-meshheading:15885854-Disease Progression, pubmed-meshheading:15885854-Down-Regulation, pubmed-meshheading:15885854-Energy Metabolism, pubmed-meshheading:15885854-Intercellular Adhesion Molecule-1, pubmed-meshheading:15885854-Male, pubmed-meshheading:15885854-Mice, pubmed-meshheading:15885854-Mice, Knockout, pubmed-meshheading:15885854-Microglia, pubmed-meshheading:15885854-Nerve Degeneration, pubmed-meshheading:15885854-Nerve Tissue Proteins, pubmed-meshheading:15885854-Nuclear Proteins, pubmed-meshheading:15885854-Oxidative Phosphorylation, pubmed-meshheading:15885854-Thiamine Deficiency, pubmed-meshheading:15885854-Time Factors, pubmed-meshheading:15885854-Up-Regulation
pubmed:year
2005
pubmed:articleTitle
CD40-CD40L interactions promote neuronal death in a model of neurodegeneration due to mild impairment of oxidative metabolism.
pubmed:affiliation
Department of Neurology and Neuroscience, Weill Medical College of Cornell University, New York, NY, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural