INVESTIGADORES
MURER Mario Gustavo
congresos y reuniones científicas
Título:
DOES MTOR PLAY A ROLE IN THE GENERATION OF LEVODOPA-INDUCED DYSKINESIAS
Autor/es:
SABORIDO M; LARRAMENDY C; TARAVINI IRE; NEIMAN G; MURER MG; GERSHANIK OS
Lugar:
Cordoba
Reunión:
Congreso; I reunion Conjunta de Neurociencia; 2009
Institución organizadora:
Sociedad Argentina de Investigación en Neurociencia
Resumen:
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) involves profound
and persistent molecular changes in the striatum. However the intimate
mechanisms that underlie LID are poorly understood. Strong evidence
also suggests alterations in the induction phase of corticostriatal long
term potentiation (LTP) and depotentiation in LID. It is known that
LTP involves processes requiring protein synthesis. In view of this, 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
LID. Mammalian target of rapamycin (mTOR) is a serine-threonine protein
kinase that modulates cell growth, proliferation and synaptic plasticity via
the regulation of protein synthesis. To understand some of the molecular
factors and mechanisms involved in the development of LID we inhibited
mTOR during sensitization to levodopa. To that effect, 22-gauge stainless steel cannulae were implanted hemilaterally in the striatum of 6-OHDA lesioned rats. Rats received 0.5 µl of vehicle or rapamycin (30, 60 and 120 nM) 15 min before levodopa (25 mg/kg), once every 48 h for a total of three times (sensitization). Two days after that, both groups received 25mg/kg levodopa. Contralateral rotations, dyskinesias and the use of the contralateral forelimb were tested. We found no significant differences in dyskinesia score between vehicle and rapamycin treated animals. This preliminary data suggests that mTOR is probably not involved in th e molecular changes that lead to the development of LID in an animal model of parkinsonism.