Linked Life Data

9822742

Source:http://linkedlifedata.com/resource/pubmed/id/9822742

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
23
pubmed:dateCreated
1998-12-18
pubmed:abstractText
Neuronal degeneration and cell death can result from excessive activation of receptors for the excitatory neurotransmitter glutamate; however, the very earliest changes in cytoskeletal organization have not been well documented. We have used an in vitro model system to examine the early consequences of intense glutamate receptor activation on dendritic spine synapses. Cultured hippocampal neurons exposed to NMDA for as little as 5 min exhibited a rapid and extensive loss of dendritic spines. Staining for the presynaptic marker synapsin 1 and the postsynaptic density proteins PSD-95 and the NR1 subunit of NMDA receptors remained intact. The disappearance of spines was accompanied by a selective loss of filamentous actin staining at synapses. The NMDA-induced loss of spine actin was time- and concentration-dependent and blocked by NMDA receptor antagonists. The effect was mimicked by L-glutamate, AMPA, and ionomycin but not by agonists of L-type calcium channels or of metabotropic glutamate receptors. The effect of NMDA on local actin assembly was strongly attenuated by pretreatment with an actin stabilizing compound or by an antagonist of the calcium-dependent protein phosphatase calcineurin. Immunoreactivity for calcineurin was enriched at synapses together with F-actin. These results indicate that the actin-mediated stability of synaptic structure is disrupted by intense glutamate receptor activity and that calcineurin blockers may be useful in preventing such destabilization.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Dec
pubmed:issn
0270-6474
pubmed:author
pubmed:issnType
Print
pubmed:day
1
pubmed:volume
18
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
9835-44
pubmed:dateRevised
2008-11-21
pubmed:meshHeading
pubmed:year
1998
pubmed:articleTitle
Regulation of F-actin stability in dendritic spines by glutamate receptors and calcineurin.
pubmed:affiliation
Department of Cell Biology, The Scripps Research Institute, La Jolla, California 92037, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S.