Subcellular redistribution of the synapse-associated proteins PSD-95 and SAP97 in animal models of Parkinson's disease and L-DOPA-induced dyskinesia.
FASEB J
; 19(6): 583-5, 2005 Apr.
Article
en En
| MEDLINE
| ID: mdl-15703272
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.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Enfermedad de Parkinson Secundaria
/
Fracciones Subcelulares
/
Sinapsis
/
Discinesias
/
Péptidos y Proteínas de Señalización Intracelular
/
Proteínas Adaptadoras Transductoras de Señales
/
Proteínas de la Membrana
Tipo de estudio:
Etiology_studies
/
Risk_factors_studies
Límite:
Animals
Idioma:
En
Revista:
FASEB J
Asunto de la revista:
BIOLOGIA
/
FISIOLOGIA
Año:
2005
Tipo del documento:
Article
País de afiliación:
Canadá