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The Journal of Neuroscience, December 15, 2001, 21(24):9888-9895

Functional Regeneration in a Rat Parkinson's Model after Intrastriatal Grafts of Glial Cell Line-Derived Neurotrophic Factor and Transforming Growth Factor ₁-Expressing Extra-Adrenal Chromaffin Cells of the Zuckerkandl's Organ

Emilio Fernandez Espejo¹, M. Carmen Gonzalez-Albo², Joao-Paulo Moraes¹, Fadwa El Banoua¹, Juan A. Flores¹, and Isabel Caraballo¹

¹ Departamento de Fisiologia Medica y Biofisica, Universidad de Sevilla, E-41009 Sevilla, Spain, and ² Instituto Cajal, Consejo Superior de Investigaciones Cientificas, E-28002 Madrid, Spain

Intrabrain transplantation of chromaffin cell aggregates of the Zuckerkandl's organ, an extra-adrenal paraganglion that has never been tested for antiparkinsonian treatment, induced gradual improvement of functional deficits in parkinsonian rats. These beneficial effects were related to long survival of grafted cells, striatal reinnervation, and enhancement of dopamine levels in grafted striatum. Grafted cells were not dopaminergics, but they expressed glial cell line-derived neurotrophic factor (GDNF) and transforming growth factor-₁. These factors were detected in the host striatal tissue, indicating that chromaffin cells secreted them after grafting. Because glial cell line-derived neurotrophic factor possesses neurorestorative properties over dopaminergic neurons, and transforming growth factor-₁ is a cofactor that potentiates the neurotrophic actions of GDNF, functional regeneration was likely caused by the chronic trophic action of neurotrophic factors delivered by long-surviving grafted cells. This work should stimulate research on the clinical applicability of transplants of the Zuckerkandl's organ in Parkinson's disease.

Key words: Parkinson's disease; graft; Zuckerkandl's organ; extra-adrenal cell; adrenal cell; glial cell line-derived neurotrophic factor; transforming growth factor-₁; stereology; 6-hydroxydopamine

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Copyright © 2001 Society for Neuroscience  0270-6474/01/21249888-08$05.00/0

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