INTR10

Authors:

Garcia J, Hahn M, Timmer M, Papazoglou A, Nikkhah G

Institutions:

Dept. of Stereotactic Neurosurgery, Laboratory of Molecular Neurosurgery, Neurocentre, University Hospital Freiburg. Breisacher Str. 64, 79106 Freiburg, Germany

Title of abstract : Distinctive pattern of anatomical maturation and functional integration of dopaminergic progenitor cells following transplantation in a rat model of Parkinson’s disease

Abstract text:

The restorative capacity of dopaminergic (DA) transplants is determined by DA neurogenesis, migration,TH-positive fibre reinnervation, host-derived anatomical and functional influences. Here we examined the impact of graft-host interactions on the survival and functional capacity of DA progenitor cells in rats with unilateral 6-hydroxydopamine lesions. DA transplant-induced functional recovery was observed in postural balancing reactions already after 10 days and in stepping behaviour after 13 days, , and later, after 16 days, in the amphetamine-induced rotation test. Three distinct patterns of functional recovery could be observed at 6 to 9 weeks post-transplantation. Firstly, behavioural improvements in drug-induced rotational asymmetry, stepping and skilled forelimb behaviour were directly related to DA neuron survival and TH-positive fibre reinnervation. Secondly, recovery in postural balancing reactions was closely related to a specific developmental time window of donor age, e.g. only seen in embryonic day (E) 13 (9-10mm) and E14 (11-12 mm) grafts. Finally, no functional graft effects were seen in the table lift test. Interestingly, DA neuron graft survival, TH-positive fibre outgrowth and graft volumen were significantly influenced by the developmental time window in which the DA progenitor cells were dissected from the ventral mesencephalon, i.e. from E12 (7-8mm), E13 (9-10mm), E14 (11-12 mm) or E15 (13-14 mm)old rat embryos.

These data highlight the complexity of DA graft-host interactions and provides novel insights into the dynamics of DA progenitor graft-mediated functional recovery in animal models of Parkinson’s disease.

This entry was posted on Monday, August 4th, 2008 at 16:12 and is filed under PD: models and applications, all. You can follow any responses to this entry through the RSS 2.0 feed. Responses are currently closed, but you can trackback from your own site.