This subproject is one of many research subprojects utilizing the resources provided by a Center grant funded by NIH/NCRR. Primary support for the subproject and the subproject's principal investigator may have been provided by other sources, including other NIH sources. The Total Cost listed for the subproject likely represents the estimated amount of Center infrastructure utilized by the subproject, not direct funding provided by the NCRR grant to the subproject or subproject staff. Dystonia is a disabling condition with unsatisfactory treatment choices. Motivated by the observation that dystonia (and not parkinsonism) frequently accompanies states of disturbed dopamine metabolism in young patients, these studies assess the effects of dopamine depletion in infant monkeys. During the reporting period, we completed observations in three infant monkeys which were treated with weekly injections of MPTP. Despite the fact that the cumulative MPTP doses surpassed those used in older animals for the induction of parkinsonism threefold, the animals did not develop significant parkinsonism or dystonia. We also studied two additional younger animals which were treated with higher doses of MPTP over the course of one month. Both developed intermittent neck, trunk and extremity dystonia. One of them also developed mild parkinsonism. As is typical for dystonia, behavioral activation exacerbated abnormal posturing. In the animal that developed parkinsonism, this was weakly correlated with the severity of dystonia. We are still analyzing the histological results. A study of markers of dopamine depletion (stains for tyrosine hydroxylase and the dopamine transporter) showed that symptomatic monkeys showed more pronounced striatal dopaminergic loss than asymptomatic monkeys and that the loss of striatal dopaminergic innervation in the infant monkeys with dystonia was at least as severe as that in parkinsonian adult animals. These results provide evidence that dopamine depletion can lead to dystonia when the depleting intervention occurs at a very young age. We are currently in the process of studying the distribution of cholinergic and serotonergic markers in these animals.
Showing the most recent 10 out of 912 publications
