Motor-training-specific improvement of morphological and functional integration of dopaminergic intrastriatal grafts in the 6-OHDA rat model of Parkinson’s disease

A. Klein, V. Kloth, A. Papazoglou, and G. Nikkhah

Laboratory of Molecular Neurosurgery; Department of Stereotactic Neurosurgery, University Hospital Freiburg, Neurocentre, Freiburg; Germany

Parkinson’s disease (PD) is one of the most common neurodegenerative diseases and leads to severe motor and cognitive impairments. It is mainly caused by the degeneration of the dopaminergic cells within the nigrostriatal pathway. To substitute this loss of cells and their functions cell replacement approaches have been established in the past but -despite some raising hope to achieve recovery in animal models and clinical trials- they all failed to restore and rewire the basal ganglia circuitry completely. In the 6-hydroxydopamine (6-OHDA) rat model of PD we could previously show that the survival of ectopic grafts of rat embryonic day 14 neural progenitor cells derived from the ventral mesencephalon can dramatically be influenced by motor training (e.g. with increasing training up to 62% enhanced cell survival after grafting). Intermittent and repeated physical exercises improved not only the survival but also the functional integration of grafted cells within the host tissue. In the present study, we want to examine which speci.c motor training enhances functional recovery after transplantation of dopaminergic cells in hemiparkinsonian rats. Five groups of Sprague Dawley rats were lesioned and transplanted (1. enriched environment housed rats, 2. rats trained in spontaneous behavior, 3. rats trained in the paw-reaching-task, 4. rats trained only in the forced choice paw-reaching-task, 5. rats that had voluntary access to a running wheel); there were two control groups (1. healthy rats, 2. lesioned but sham-transplanted rats). Lesion and graft effects were evaluated by drug-induced rotation. Graft survival, graft volume and fibre density will be assessed by immunocytochemistry and BrdU labelling. This is an ongoing study and further results will be presented at the conference. Our previous results and the present study may highlight the neuromodulatory effects of environmental stimuli and sensorimotor exercise on dopaminergic graft survival and function which may ultimately lead to the optimization of clinical transplantation trials in PD.

Paper presented at Measuring Behavior 2005 , 5^th International Conference on Methods and Techniques in Behavioral Research, 30 August - 2 September 2005, Wageningen, The Netherlands.

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