Linked Life Data

15703272

Source:http://linkedlifedata.com/resource/pubmed/id/15703272

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
6
pubmed:dateCreated
2005-3-25
pubmed:abstractText
Abnormalities in subcellular localization and interaction between receptors and their signaling molecules occur within the striatum in Parkinson's disease (PD) and L-DOPA-induced dyskinesia (LID). Synapse-associated proteins (SAPs), for example, PSD-95 and SAP97 organize the molecular architecture of synapses and regulate interactions between receptors and downstream-signaling molecules. Here, we show that expression and subcellular distribution of PSD-95 and SAP97 are altered in the striatum of unilateral 6-OHDA-lesioned rats following repeated vehicle (a model of PD) or L-DOPA administration (a model of L-DOPA-induced dyskinesia). Furthermore, following dopamine-depletion and development of behavioral deficits in Rotorod performance, indicative of parkinsonism, we observed a dramatic decrease in total striatal levels of PSD-95 and SAP97 (to 25.6 +/- 9.9% and 19.0 +/- 5.0% of control, respectively). The remaining proteins were redistributed from the synapse into vesicular compartments. L-DOPA (6.5mg/kg twice a day, 21 days) induced a rotational response, which became markedly enhanced with repeated treatment (day 1: -15.8+/-7.3 rotations cf day 21: 758.2+/-114.0 rotations). Post L-DOPA treatment, PSD-95 and SAP97 levels increased (367.4 +/- 43.2% and 159.9 +/- 9.5% from control values, respectively), with both being redistributed toward synaptic membranes from vesicular compartments. In situ hybridization showed that changes in total levels of PSD-95, but not SAP97, were accompanied by qualitatively similar changes in mRNA. These data highlight the potential role of abnormalities in the subcellular distribution of SAPs in the pathophysiology of a neurological disease.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Apr
pubmed:issn
1530-6860
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
583-5
pubmed:dateRevised
2006-11-15
pubmed:meshHeading
pubmed-meshheading:15703272-Adaptor Proteins, Signal Transducing, pubmed-meshheading:15703272-Animals, pubmed-meshheading:15703272-Behavior, Animal, pubmed-meshheading:15703272-Brain, pubmed-meshheading:15703272-Brain Chemistry, pubmed-meshheading:15703272-Cell Membrane, pubmed-meshheading:15703272-Corpus Striatum, pubmed-meshheading:15703272-Disease Models, Animal, pubmed-meshheading:15703272-Dyskinesias, pubmed-meshheading:15703272-Intracellular Signaling Peptides and Proteins, pubmed-meshheading:15703272-Levodopa, pubmed-meshheading:15703272-Male, pubmed-meshheading:15703272-Membrane Proteins, pubmed-meshheading:15703272-Oxidopamine, pubmed-meshheading:15703272-Parkinson Disease, Secondary, pubmed-meshheading:15703272-RNA, Messenger, pubmed-meshheading:15703272-Rats, pubmed-meshheading:15703272-Rats, Sprague-Dawley, pubmed-meshheading:15703272-Subcellular Fractions, pubmed-meshheading:15703272-Synapses
pubmed:year
2005
pubmed:articleTitle
Subcellular redistribution of the synapse-associated proteins PSD-95 and SAP97 in animal models of Parkinson's disease and L-DOPA-induced dyskinesia.
pubmed:affiliation
Toronto Western Research Institute, Toronto Western Hospital, Toronto, Ontario, Canada. jnash@uhnres.utoronto.ca
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't