INVESTIGADORES
TARAVINI Irene Rita Eloisa
congresos y reuniones científicas
Título:
Protein synthesis inhibition effects on dyskinesia induction
Autor/es:
SABORIDO MD; LARRAMENDY C; TARAVINI IR; MURER MG; GERSHANIK OS
Lugar:
París, Francia
Reunión:
Congreso; 13th International Congress of Parkinson's Disease and Movement Disorders; 2009
Institución organizadora:
The Movement Disorder Society
Resumen:
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Dyskinesias are one of the major limiting side effects
encountered in the treatment of Parkinsons disease. Increasing data suggest
that the development of levodopa induced dyskinesias (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. As a
first approach to understand some of the molecular factors and mechanisms
involved in the development of LID we inhibited protein synthesis during sensitization to apomorphine. To that effect, 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. We found
that anisomycin-treated animals display less dyskinesias than vehicle-treated
animals (p<0.05). 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.