Article
Motor training enhances morphological restoration and functional integration of dopaminergic transplants following unilateral 6-OHDA lesion
Training fördert Überleben und funktionelle Integration dopaminerger, nigraler Transplantate nach Läsion mit 6-OHDA
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Published: | April 23, 2004 |
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Outline
Text
Objective
We investigated the impact of motor training on functional recovery and morphological restoration through nigral E14 transplants after unilateral MFB-lesion with 6-OHDA in the rat model of Parkinson´s Disease.
Methods
Nine groups of 15 rats each were included into a training programme with varying training schedules in simple and complex motor tasks. Training was applied prior to lesion, two and three months post-lesion, in the first month post-grafting and in the third month post-grafting. At each time point, two new groups were introduced to the training scheme, one „ lesion + graft group“ and one „lesion-only group“. Each training session included five days of simple motor tests, i.e. postural balance test, tabelift test, and stepping test, followed by nine days of training for skilled forelimb use in the staircase test. Healthy animals served as non-treated controls. Following behavioural assessment, the brains were immunofixed with PFA, and after Th+ immunostaining, morphological analysis of graft survival, graft volume, and fibre density followed. Statistical analysis was performed with ANOVA post hoc Bonferroni-Dunnett test (alpha-value = 5%).
Results
Results of complex motor tests revealed significant impairments in all lesioned groups, but more pronounced in animals trained post-lesion compared to pre-lesion trained animals. After transplantation, a significant graft-induced recovery from lesion impairment was seen only in prelesion (p < 0.0001) animals, a trend towards recovery in postlesion trained animals (p = 0.0001), and no recovery in animals that had received their first training after transplantation as assessed with ANOVA post hoc Bonferroni-Dunnett test (significance level p < 0.0001). On the contrary, in simple motor tasks, grafted animals with no training until three months post-grafting showed the most pronounced, yet incomplete recovery. Graft survival as measured by the number of Th+ neurons was significantly improved in prelesion trained animals in comparison to animals receiving their first training short-term post grafting (graftsurvival +44.1%; p = 0.0079) or long-term post grafting (graftsurvival +62.6%; p= 0.0061) as assessed with ANOVA post hoc Bonferroni-Dunnett test (significance level p < 0.0083). The impact of training on graft volume and fibre density is currently analysed and will be presented.
Conclusions
Prelesion motor training can significantly improve survival and functional integration of dopaminergic nigral grafts into the lesioned striatum in a rat model of Parkinson’s disease.