Effects of GDNF pretreatment on function and survival of transplanted fetal ventral mesencephalic cells in the 6-OHDA rat model of Parkinson's disease

Andereggen, Lukas; Meyer, Morten; Guzman, Raphael; Ducray, Angélique; Widmer, Hans Rudolf (2009). Effects of GDNF pretreatment on function and survival of transplanted fetal ventral mesencephalic cells in the 6-OHDA rat model of Parkinson's disease. Brain research, 1276, pp. 39-49. Amsterdam: Elsevier 10.1016/j.brainres.2009.04.021

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Transplantation of fetal dopaminergic (DA) neurons offers an experimental therapy for Parkinson's disease (PD). The low availability and the poor survival and integration of transplanted cells in the host brain are major obstacles in this approach. Glial cell line-derived neurotrophic factor (GDNF) is a potent neurotrophic factor with growth- and survival-promoting capabilities for developing DA neurons. In the present study, we examined whether pretreatment of ventral mesencephalic (VM) free-floating roller tube (FFRT) cultures with GDNF would improve graft survival and function. For that purpose organotypic cultures of E14 rat VM were grown for 2, 4 or 8 days in the absence (control) or presence of GDNF [10 ng/ml] and transplanted into the striatum of 6-hydroxydopamine-lesioned rats. While all groups of rats showed a significant reduction in d-amphetamine-induced rotations at 6 weeks posttransplantation a significantly improved graft function was observed only in the days in vitro (DIV) 4 GDNF pretreated group compared to the control group. In addition, no statistical significant differences between groups were found in the number of surviving tyrosine hydroxylase-immunoreactive (TH-ir) neurons assessed at 9 weeks posttransplantation. However, a tendency for higher TH-ir fiber outgrowth from the transplants in the GDNF pretreated groups as compared to corresponding controls was observed. Furthermore, GDNF pretreatment showed a tendency for a higher number of GIRK2 positive neurons in the grafts. In sum, our findings demonstrate that GDNF pretreatment was not disadvantageous for transplants of embryonic rat VM with the FFRT culture technique but only marginally improved graft survival and function.

Item Type:	Journal Article (Original Article)
Division/Institute:	04 Faculty of Medicine > Department of Head Organs and Neurology (DKNS) > Clinic of Neurosurgery
UniBE Contributor:	Andereggen, Lukas, Ducray, Angélique, Widmer, Hans Rudolf
Subjects:	600 Technology > 610 Medicine & health
ISSN:	0006-8993
Publisher:	Elsevier
Language:	English
Submitter:	Factscience Import
Date Deposited:	04 Oct 2013 15:13
Last Modified:	05 Dec 2022 14:22
Publisher DOI:	10.1016/j.brainres.2009.04.021
PubMed ID:	19389387
Web of Science ID:	000267516700005
URI:	https://boris.unibe.ch/id/eprint/32027 (FactScience: 196855)