Linked Life Data

19136940

Source:http://linkedlifedata.com/resource/pubmed/id/19136940

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2009-3-16
pubmed:abstractText
Positive alpha-amino-3-hydroxy-5-methylisoxazole-4-propionic acid (AMPA) receptor modulators include benzamide compounds that allosterically modulate AMPA glutamate receptors. These small molecules that cross the blood-brain barrier have been shown to act as a neuroprotectant by increasing the levels of endogenous brain-derived neurotrophic factor (BDNF). Positive AMPA receptor modulators have also been shown to increase the levels of growth-associated protein-43 (GAP-43). GAP-43 plays a major role in many aspects of neuronal function in vertebrates. The goal of this study was to determine whether GAP-43 was important in mediating the actions of positive AMPA receptor modulator (S18986) and BDNF. Using cortical cultures from GAP-43 knockout and control mice, we show that (1) GAP-43 is upregulated in response to S18986 and BDNF in control cultures; (2) this upregulation of GAP-43 is essential for mediating the neuroprotective effects of S18986 and BDNF; (3) administration of S18986 and BDNF leads to an increase in the expression of the glutamate transporters GLT-1 and GLAST that are key to limiting excitotoxic cell death and this increase in GLT-1 and GLAST expression is completely blocked in the absence of GAP-43. Taken together this study concludes that GAP-43 is an important mediator of the neurotrophic effects of S18986 and BDNF on neuronal survival and plasticity, and is essential for the success of positive AMPA receptor modulator-BDNF-based neurotrophin therapy.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1476-5403
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
16
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
624-37
pubmed:meshHeading
pubmed-meshheading:19136940-Animals, pubmed-meshheading:19136940-Benzothiadiazines, pubmed-meshheading:19136940-Blotting, Western, pubmed-meshheading:19136940-Brain-Derived Neurotrophic Factor, pubmed-meshheading:19136940-Cell Death, pubmed-meshheading:19136940-Cells, Cultured, pubmed-meshheading:19136940-Cerebral Cortex, pubmed-meshheading:19136940-GAP-43 Protein, pubmed-meshheading:19136940-Gene Expression Regulation, pubmed-meshheading:19136940-Immunohistochemistry, pubmed-meshheading:19136940-In Situ Nick-End Labeling, pubmed-meshheading:19136940-Mice, pubmed-meshheading:19136940-Mice, Knockout, pubmed-meshheading:19136940-Neuroprotective Agents, pubmed-meshheading:19136940-Polymerase Chain Reaction, pubmed-meshheading:19136940-Reactive Oxygen Species, pubmed-meshheading:19136940-Receptors, AMPA
pubmed:year
2009
pubmed:articleTitle
GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986.
pubmed:affiliation
National Brain Research Center, Manesar, Haryana, India.
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't