Linked Life Data

11161628

Source:http://linkedlifedata.com/resource/pubmed/id/11161628

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
2
pubmed:dateCreated
2001-2-22
pubmed:abstractText
There is growing evidence that mitochondrial dysfunction is an important factor in a cascade of neurotoxic events as observed during pathogenesis of various neurodegenerative diseases. In the neurodegenerative disease amyotrophic lateral sclerosis (ALS) both spinal and cortical motoneurons degenerate, but in experimental studies most attention so far has been focussed on the spinal motoneurons. In order to study the role of mitochondrial dysfunction in the pathways leading to cortical (upper) motoneuron (CMN) death, a long-term culture system of rat cortical explants was used. CMNs were visualized by immunocytochemical labeling with antibodies directed against nonphosphorylated neurofilament, SMI-32, and for their identification we also used their location in layer V of the explant, their size, and their morphological appearance. In this model the effect of mitochondrial inhibition was studied through chronic malonate treatment. For 2 weeks, low doses of complex II inhibitor malonate were added to the cultures twice a week. The malonate-induced chronic mitochondrial inhibition resulted in a dose-dependent increase of CMN death in the slices. Neuroprotection was achieved with the NMDA antagonist MK-801 and the non-NMDA antagonist CNQX indicating the involvement of glutamate in the malonate-induced CMN death. Furthermore, our data indicate that chronic mitochondrial inhibition results in CMN death, which is mediated by glutamate excitotoxicity via both non-NMDA and NMDA receptors. In this respect the present in vitro approach may act as a model for understanding mechanisms underlying CMN death in ALS.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Feb
pubmed:issn
0014-4886
pubmed:author
pubmed:copyrightInfo
Copyright 2001 Academic Press.
pubmed:issnType
Print
pubmed:volume
167
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
393-400
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:11161628-Animals, pubmed-meshheading:11161628-Antigens, Differentiation, pubmed-meshheading:11161628-Cell Death, pubmed-meshheading:11161628-Cell Size, pubmed-meshheading:11161628-Cells, Cultured, pubmed-meshheading:11161628-Cerebral Cortex, pubmed-meshheading:11161628-Dizocilpine Maleate, pubmed-meshheading:11161628-Dose-Response Relationship, Drug, pubmed-meshheading:11161628-Excitatory Amino Acid Antagonists, pubmed-meshheading:11161628-Glutamic Acid, pubmed-meshheading:11161628-Immunohistochemistry, pubmed-meshheading:11161628-Malonates, pubmed-meshheading:11161628-Mitochondria, pubmed-meshheading:11161628-Models, Biological, pubmed-meshheading:11161628-Motor Neurons, pubmed-meshheading:11161628-Neurodegenerative Diseases, pubmed-meshheading:11161628-Neurofilament Proteins, pubmed-meshheading:11161628-Neuroprotective Agents, pubmed-meshheading:11161628-Pyramidal Cells, pubmed-meshheading:11161628-Rats, pubmed-meshheading:11161628-Rats, Wistar, pubmed-meshheading:11161628-Time Factors
pubmed:year
2001
pubmed:articleTitle
Chronic mitochondrial inhibition induces glutamate-mediated corticomotoneuron death in an organotypic culture model.
pubmed:affiliation
Department of Experimental Neurology, RMI for Neurosciences, UMC Utrecht, 3508 GA, Utrecht, The Netherlands. m.g.h.vanwesterlaak@neuro.azu.nl
pubmed:publicationType
Journal Article, In Vitro