gms | German Medical Science

Objective: Sensorimotor impairments are the leading symptoms of Parkinson’s disease (PD), which is caused by the degeneration of the dopaminergic (DAergic) cells within the nigrostriatal pathway. To substitute the loss of these cells and their functions cell replacement strategies have been established in the past, but no optimal therapeutical protocol has been achieved yet, neither in animal models nor in clinical trials. Physical exercise has been proven as beneficial in terms of increased adult neurogenesis and in terms of improved survival of foetal, ectopic, and DAergic grafts (e.g. with increasing training up to 62% enhanced cell survival after transplantation). Additionally, intermittent and repeated physical exercises improved not only the survival rate but also the functional integration of grafted cells within the host tissue. In this study, we examine which specific motor training enhances functional recovery after transplantation of DAergic cells (E14 VM derived) in hemiparkinsonian rats.

Methods: Five groups of rats were lesioned and transplanted: 1. enriched environment housed rats, 2. rats trained in spontaneous behaviour, 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 three control groups with standard housing and no behavioural tests: 1. healthy rats, 2. lesioned but sham-transplanted rats, 3. lesioned and transplanted rats. Lesion and graft effects were evaluated by drug-induced rotation. Graft survival, graft volume, fibre density and neurogenesis will be assessed by immunocytochemistry and BrdU labelling.

Results: Preliminary results reveal that all animals showed overcompensation in amphetamine rotation and that the enriched environment conditions were able to reduce the overcompensatory response compared to the other housing methods. Intensive training in the spontaneous behaviour test and the paw reaching task could significantly improve the motor performance.

Conclusions: The main focus of this ongoing study is to find out if there are specific motor tests which promote best the functional recovery in hemiparkinsonian rats, or if general exercise is sufficient for convalescence after transplantation of E14 progenitor cells. Together with our previous results the outcome of this study may be taken into consideration for future clinical trials and prove that physical exercise can promote the functional recovery induced by cell replacement strategies.