Linked Life Data

12614342

Source:http://linkedlifedata.com/resource/pubmed/id/12614342

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2003-3-4
pubmed:abstractText
The survival promoting and neuroprotective actions of brain-derived neurotrophic factor (BDNF) are well known but under certain circumstances this growth factor can also exacerbate excitotoxic insults to neurons. Prior exploration of the receptor through which BDNF exerts this action on motor neurons deflects attention away from p75. Here we investigated the possibility that BDNF acts through the receptor tyrosine kinase, TrkB, to confer on motor neurons sensitivity to excitotoxic challenge. We blocked BDNF activation of TrkB using a dominant negative TrkB mutant or a TrkB function blocking antibody, and found that this protected motor neurons against excitotoxic insult in cultures of mixed spinal cord neurons. Addition of a function blocking antibody to BDNF to mixed spinal cord neuron cultures is also neuroprotective indicating that endogenously produced BDNF participates in vulnerability to excitotoxicity. We next examined the intracellular signaling cascades that are engaged upon TrkB activation. Previously we found that inhibition of the phosphatidylinositide-3'-kinase (PI3'K) pathway blocks BDNF-induced excitotoxic sensitivity. Here we show that expression of a constitutively active catalytic subunit of PI3'K, p110, confers excitotoxic sensitivity (ES) upon motor neurons not incubated with BDNF. Parallel studies with purified motor neurons confirm that these events are likely to be occuring specifically within motor neurons. The abrogation of BDNF's capacity to accentuate excitotoxic insults may make it a more attractive neuroprotective agent.
pubmed:grant
pubmed:keyword
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
0022-3042
pubmed:author
pubmed:issnType
Print
pubmed:volume
84
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1421-30
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed-meshheading:12614342-Animals, pubmed-meshheading:12614342-Antibodies, pubmed-meshheading:12614342-Brain-Derived Neurotrophic Factor, pubmed-meshheading:12614342-Catalytic Domain, pubmed-meshheading:12614342-Cells, Cultured, pubmed-meshheading:12614342-Dose-Response Relationship, Drug, pubmed-meshheading:12614342-Gene Transfer Techniques, pubmed-meshheading:12614342-Genes, Dominant, pubmed-meshheading:12614342-Motor Neurons, pubmed-meshheading:12614342-Neuroprotective Agents, pubmed-meshheading:12614342-Neurotoxins, pubmed-meshheading:12614342-Phosphatidylinositol 3-Kinases, pubmed-meshheading:12614342-Rats, pubmed-meshheading:12614342-Rats, Sprague-Dawley, pubmed-meshheading:12614342-Receptor, trkB, pubmed-meshheading:12614342-Signal Transduction, pubmed-meshheading:12614342-Spinal Cord
pubmed:year
2003
pubmed:articleTitle
BDNF heightens the sensitivity of motor neurons to excitotoxic insults through activation of TrkB.
pubmed:affiliation
Department of Neurology, Yale University School of Medicine, New Haven, Connecticut, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, U.S. Gov't, Non-P.H.S.