INTR10

Authors:

Fernandez-Espejo E 1, Galan-Rodriguez B 1, del-Marco A 1, Ramiro-Fuentes S 1, Gonzalez-Aparicio R 1, Tunez I 2, Tasset I 2

Institutions:

1. Departamento de Fisiologia Medica y Biofisica, Universidad de Sevilla, 41009 Sevilla, Spain.
2. Departamento de Bioquimica y Biologia Molecular, Universidad de Cordoba, Av. Menendez Pidal s/n, 14004 Cordoba, Spain.

Title of abstract : Antiparkinsonian trophic effects of grafts of aggregated extra-adrenal chromaffin cells in rats

Abstract text:

The objective was to discern the neuroregenerative effects of grafts of extra-adrenal cells of the Zuckerkandl’s paraganglion (ZP) on the nigro-striatal circuit, by using the retrograde model of parkinsonism in rats. The antiparkinsonian efficacy of two types of grafting procedures was studied (cell aggregates versus dispersed cells), and GDNF and TGFbeta1 (dopaminotrophic factors) as well as dopamine presence in extra-adrenal tissue was analysed. Extra-adrenal chromaffin cells are noradrenergics (TH+/DBH+/PNMT-), tissue dopamine is low, and they express both GDNF and TGFbeta1. Grafts of cell aggregates, not of dispersed cells, exerted a trophic regeneration of the host striatum, leading to amelioration of motor deficits. Sprouting of spared dopaminergic fibers within the striatum, reduction of dopamine axon degeneration, and/or enhanced phenotypic expression of TH would explain striatal regeneration. Grafted cells as aggregates showed a better survival rate than dispersed cells (1% vs. 0.15%), and they express higher levels of GDNF. Higher survivality and GDNF content together with the neurorestorative and dopaminotrophic action of both GDNF and TGFbeta1 could account for striatal recovery and functional amelioration after grafting ZP cell aggregates. Finally, nigral degeneration and partial degeneration of ventral tegmental area were not precluded after transplantation, indicating that the trophic effect of grafts was local within the host striatum.
Supported by grants to EFE from Junta de Andalucia (CVI127, and Proyectos de Excelencia, EXC/2006/CVI127-1716), and Red de Terapia Celular (Instituto Carlos III, RD06).

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