Article
A matter of restoration or compensation? The potential of embryonic dopaminergic grafts in hemiparkinsonian rats on skilled limb movements and gait performance
Restauration oder Kompensation? Das Potential embryonaler, dopaminerger Transplantate auf komplexe Greifbewegungen und das Laufverhalten im Tiermodell der Parkinsonschen Krankheit
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Authors
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Alexander Klein
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg - Neurozentrum, Freiburg
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G. A. Metz
- Canadian Centre for Behavioural Neuroscience, University of Lethbridge, Lethbridge /CDN
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J. Wessolleck
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg - Neurozentrum, Freiburg
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A. Papazoglou
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg - Neurozentrum, Freiburg
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M. Knieling
- Universitätsklinikum Jena, Abt. für Neurologie, Jena
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G. Nikkhah
- Labor für Molekulare Neurochirurgie, Abt. für Funktionelle und Stereotaktische Neurochirurgie, Universitätsklinikum Freiburg - Neurozentrum, Freiburg
| Published: | April 23, 2004 |
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Outline
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Objective
The aim of the present project is to determine whether transplantation of dopaminergic neurons in a rat model of Parkinson’s disease mediates recovery in skilled limb movements and gait performance by rewiring neural motor pattern for grasping movements and limb coordination, or whether transplants support compensation of motor deficits.
Methods
The rats were trained in skilled reaching tasks (staircase test, single pellet grasping task). The rung walking task and footprint analysis were performed to test skilled walking and forelimb/hindlimb coordination. 21 animals received a unilateral MFB lesion with 6-OHDA, eight served as unlesioned controls. Thirteen weeks after the lesion, thirteen rats with MFB lesion were transplanted intrastriatally with DAergic grafts from foetal ventral mesencephalon and eight animals received sham transplantation surgery. Rotational behaviour after apomorphine and amphetamine injections was assessed after each surgery procedure. Testing in the skilled reaching tasks, the rung walking task and footprint analysis continued throughout the experiment and was video recorded. Histological analysis of the brains was performed and nigral tyrosinhydroxylase positive cells were counted to assess lesion severity and survival of transplanted cells.
Results
Postlesion data demonstrated for the lesioned rats a strong increase in rotation compared to the controls for both drugs. After transplantation the grafted subjects overcompensated under amphetamine administration (+15.5rpm to -8.9rpm) and showed a significant reduction of apomorphine rotation (-12.3rpm to 5.4rpm). This indicated a strong graft survival and graft effect in simple motor behaviour. In the staircase test an improvement of “pellets eaten” could be observed between the sham-operated and grafted rats (8 pellets/sham; 13 pellets/transplanted group). The single pellet task did not show this improvement after transplantation. Footprint analysis revealed a strong lesion-induced impairment and only partially a better task performance after grafting.
Conclusions
Quantitative analysis of simple and complex motor behaviour demonstrated a significant improvement due to E14 grafts whereas a qualitative investigation of skilled limb movements revealed no effect. Therefore we conclude that in hemiparkinsonian rats the recovery in quantitative analysis -seen after grafting dopaminergic mesencephalic E14 cells- is due to compensatory mechanisms. These results are confirmed by footprint data analysis.
