15-07-08(14:18:17)
Authors:
Szcznesiak AM 1
Robertson HA 1
Institutions:
1. Brain Repair Centre, Department of Pharmacology,Dalhousie University, Halifax, NS, Canada B3H1X5
Title of abstract : Sonic hedgehog increases the survival and behavioural effects of transplanted DA neurons.
Abstract text:
Animal experimentation and open clinical trials have provided evidence that neural transplantation is effective in Parkinson’s disease (PD). However, outcomes are limited by the survival of grafted neurons, and by variable clinical outcome. Studies have suggested that co-grafting supportive cells might improve graft survival. In vivo, co-grafts of NPCs increase both survival and the effects of VM grafts in the 6-OHDA lesion rat model of PD (Rafuse et al ,2005, Neuroscience 131, 899).
We investigated the effects of co-transplantation of mouse eGFP-VM cells, with mouse wild type NPCs (Shh+/+ NPCs), or NPCs cells derived from mice with a null mutation in Shh (Shh-/- NPCs), on grafted fetal neurons.
Rats with unilateral 6-OHDA lesions were divided into six groups and received striatal grafts, with the following cell suspensions: eGFP-VMs only (50,000 or 150,000), or eGFP-VM cells (50,000 or 150,000) in combination with either 400,000 NPCs Shh+/+, or 400,000 Shh-/- NPCs. At either 2 or 6-weeks post-transplantation animals were assesses behaviourally and for survival of TH neurons.
The number of DA neurons was significantly higher in the grafts when they were co-transplanted with Shh+/+, as compared to Shh-/- NPCs or VM-only groups. Only the rats that received the VM cells in combination with 150,000 Shh+/+ NPCs had a improvement in motor behavior.
This demonstrates that the effect of NPCs was attributable to Shh and supports co-grafting to improve survival of dopaminergic neurons and the functional outcome of transplantation.
(Supported by the Parkinson Society Canada and CIHR)
