ININFA   02677
INSTITUTO DE INVESTIGACIONES FARMACOLOGICAS
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Protein synthesis inhibition effects on dyskinesia induction
Autor/es:
MARIANO SABORIDO; CELIA LARRAMENDY; IRENE TARAVINI; GUSTAVO MURER; OSCAR GERSHANIK
Lugar:
París, Francia
Reunión:
Congreso; 13th International Congress of Parkinson`s Disease and Movements disorders; 2009
Institución organizadora:
The Movement Disorder Society´s
Resumen:
&amp;amp;amp;lt;!-- /* Font Definitions */ @font-face {font-family:Tahoma; panose-1:2 11 6 4 3 5 4 4 2 4; mso-font-charset:0; mso-generic-font-family:swiss; mso-font-pitch:variable; mso-font-signature:1627421319 -2147483648 8 0 66047 0;} /* Style Definitions */ p.MsoNormal, li.MsoNormal, div.MsoNormal {mso-style-parent:""; margin:0cm; margin-bottom:.0001pt; mso-pagination:widow-orphan; font-size:12.0pt; font-family:"Times New Roman"; mso-fareast-font-family:"Times New Roman";} @page Section1 {size:612.0pt 792.0pt; margin:70.85pt 3.0cm 70.85pt 3.0cm; mso-header-margin:36.0pt; mso-footer-margin:36.0pt; mso-paper-source:0;} div.Section1 {page:Section1;} --&amp;amp;amp;gt; Objective: As a first approach to understand some of the molecular factors and mechanisms involved in the development of levodopa induced dyskinesias (LID) we inhibited protein synthesis during sensitization to apomorphine. Background: Dyskinesias are one of the major limiting side effects encountered in the treatment of Parkinson’s disease. Increasing data suggest that the development of LID involve profound and persistent molecular changes in the striatum, including abnormal activation of ERK (extracellular activated protein kinase) and upregulation of prodynorphin mRNA and fosB/ΔfosB related transcription factors. However the intimate mechanisms that underlie these abnormal movements are poorly understood. Methods: 22-gauge stainless steel cannulae were implanted hemilaterally in the striatum of 6-OHDA lesioned rats.  Anisomycin (160µg/1.6µl), a well characterized protein synthesis inhibitor, or vehicle were infused 15 min before apomorphine (0.025mg/kg) once every 48 h for a total of three times (sensitization). Forty eight hours later, all groups received 0.05mg/kg apomorphine. After apomorphine administration contralateral rotations and dyskinesias were tested. Twenty minutes after apomorphine, akinesia of the contralateral forepaw was also tested by means of the cylinder test. Results: We found that anisomycin-treated animals display less dyskinesias than vehicle-treated animals (p<0.05). Conclusions: This preliminary data suggests that protein synthesis would be necessary for the induction of plastic changes that occur in response to dopamine agonists and lead to the development of dyskinesias in an animal model of parkinsonism. Strong evidence also suggests alterations in the induction phase of corticostriatal long term potentiation (LTP) and depotentiation in dyskinesias. It is known that  LTP involves processes requiring protein synthesis. In view of this and based on our results it is tempting to speculate that molecular factors known to be involved in plastic changes such as LTP would also play a role in the development of dyskinesias. As a logical next step we will undertake the evaluation of these factors.