04-06-08(16:23:15)
Authors:
Carlsson T 1,2
Carta M 1,2
Muñoz Ana 1
Mattsson B 1
Winkler C 3
Kirik D 2
Björklund A 1
Institutions:
1. Wallenberg Neuroscience Center, Dept. Experimental Medical Science, Lund University, BMC A11, 221 84 Lund, Sweden.
2. Brain Repair and Imaging in Neural Systems (B.R.A.I.N.S) Unit, Dept. Experimental Medical Science, Lund University, BMC D11, 221 84 Lund, Sweden.
3. Department of Neurology, Neurocentre, University of Freiburg, 79106 Freiburg, Germany.
Title of abstract : Extent of dopamine neuron degeneration determines the impact of serotonin neuron transplants on the development of L-DOPA-induced dyskinesia in a rat model of Parkinson’s disease
Abstract text:
Fetal ventral mesencephalic grafts in patients with Parkinson’s disease have shown to include serotonin neurons, and recent animal data suggests that serotonin neurons play an important role in the development of L-DOPA-induced dyskinesia. Therefore serotonin neurons may, at least in part, explain the variable outcome in the clinical transplantation trials. In this study we have evaluated intrastriatal 6-OHDA lesion rats with low-level of L-DOPA-induced dyskinesias (mimicking a early stage of the disease), which received transplants of serotonin neurons alone or in combination with dopamine neurons. After 10 weeks monitoring dyskinesias after transplantation, the animals received an additional 6-OHDA lesion now in the medial forebrain bundle in order to remove remaining dopamine fibers (mimicking a progression of the disease). The animals where further evaluated for additional changes in L-DOPA-induced dyskinesias over a two-week daily L-DOPA treatment period. Our data showed that intrastriatal dopamine lesioned rats grafted with serotonin neurons alone (that display only low-level dyskinesia at the time of grafting), induced significant worsening in the severity of dyskinesia, but they remained at a low-to-moderate level. However, removal of the remaining striatal dopamine fibers resulted in a dramatic increased in the severity of dyskinesias. Grafts containing ~2:1 ratio of dopamine and serotonin neurons, in contrast, resulted in a marked dampen in L-DOPA-induced dyskinesia over time, even after the second dopamine lesion. Here, we conclude that the extent of the striatal dopamine fiber innervation is a critical factor that determines the role of included serotonin neurons in grafts, on dyskinesia after transplantation.
