GAP-43 is essential for the neurotrophic effects of BDNF and positive AMPA receptor modulator S18986 View Full Text


Ontology type: schema:ScholarlyArticle      Open Access: True


Article Info

DATE

2009-04

AUTHORS

S K Gupta, R Mishra, S Kusum, M Spedding, K F Meiri, P Gressens, S Mani

ABSTRACT

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. More... »

PAGES

cdd2008188

References to SciGraph publications

Identifiers

URI

http://scigraph.springernature.com/pub.10.1038/cdd.2008.188

DOI

http://dx.doi.org/10.1038/cdd.2008.188

DIMENSIONS

https://app.dimensions.ai/details/publication/pub.1051961545

PUBMED

https://www.ncbi.nlm.nih.gov/pubmed/19136940


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Turtle is a human-readable linked data format.

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RDF/XML is a standard XML format for linked data.

curl -H 'Accept: application/rdf+xml' 'https://scigraph.springernature.com/pub.10.1038/cdd.2008.188'


 

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