25-07-08(14:48:00)
Authors:
Wessolleck J 1*, Klein A 1,2*, Papazoglou A 1, Metz GA 2 and Nikkhah G 1
* These authors contributed equally to this work.
Institutions:
1 Laboratory of Molecular Neurosurgery, Dept. of Stereotactic Neurosurgery, University Hospital – Neurocentre, Breisacher Str. 64, D-79106 Freiburg, Germany
2 Canadian Centre for Behavioural Neuroscience, University of Lethbridge, 4401 University Drive, Lethbridge, Alberta, T1K 3M4, Canada
Title of abstract : Influence of foetal dopaminergic progenitor cell transplantation on gait pattern in the 6-hydroxy dopamine rat model of Parkinson’s disease
Abstract text:
One of the cardinal symptoms in patients suffering from Parkinson’s disease (PD) is shuffling gait and postural imbalance. In the 6-hydroxy dopamine (6-OHDA) rat model of PD functional sensorimotor recovery following transplantation of dopaminergic (DAergic) grafts has been extensively analysed whereas the examination of gait patterns has rarely been used. The purpose of this study was to investigate the functional restoration of specific gait-related behavioural patterns such as skilled walking, balance and individual limb coordination following ectopic intrastriatal transplantation in 6-OHDA lesioned rats.
Effects of lesion and ventral mesencephalon (VM)-derived grafts were evaluated by drug-induced rotational behaviour. Walking performance was assessed by detailed footprint analysis and ladder rung walking test. Good DAergic graft survival, as revealed by immunohistochemistry, was accompanied by a compensation of drug-induced rotational asymmetries. Evaluation of walking patterns showed a heterogeneous graft-induced response both in skilled and non-skilled limb use. Grafted animals could improve their ipsi- and contralateral limb rotation and made fewer errors with their contralateral hindlimbs in comparison to sham transplanted animals. However, paw placement accuracy and the parameter distance between feet showed a delayed recovery, and the stride length was not affected by the DA grafts at all.
These findings indicate that VM-derived DAergic grafts promote recovery of gait balance and stability. It does not, however, ameliorate the shuffling gait pattern induced by 6-OHDA lesions. To achieve full recovery of locomotor patterns, techniques towards more complete, organotypic reconstruction of the nigrostriatal pathway need to be pursued.
