TY - JOUR
T1 - Grafts of extra-adrenal chromaffin cells as aggregates show better survival rate and regenerative effects on parkinsonian rats than dispersed cell grafts
AU - Galan-Rodriguez, B.
AU - del-Marco, A.
AU - Flores, J. A.
AU - Ramiro-Fuentes, S.
AU - Gonzalez-Aparicio, R.
AU - Tunez, I.
AU - Tasset, I.
AU - Fernandez-Espejo, E.
N1 - Funding Information:
Supported by grants to E.F.E. from Junta de Andalucia, Spain (CVI127, and Proyectos de Excelencia, EXC/2006/CVI127-1716) and Red de Terapia Celular (Instituto Carlos III, RD06). The authors thank Belen Rodriguez-Pedrosa and Itziar Benito for the animal care.
PY - 2008/3
Y1 - 2008/3
N2 - The objective was to discern the neuroregenerative effect of grafts of extra-adrenal cells of the Zuckerkandl's paraganglion (ZP) in the nigrostriatal circuit, by using the retrograde model of parkinsonism in rats. The antiparkinsonian efficacy of two types of grafting procedures was studied (cell aggregates vs. dispersed cells), and GDNF and TGFβ1 (dopaminotrophic factors) as well as dopamine presence in extra-adrenal tissue was analyzed. Extra-adrenal chromaffin cells are noradrenergics, tissue dopamine is low, and they express both GDNF and TGFβ1. 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, and they express higher levels of GDNF. Higher survivability and GDNF content together with the neurorestorative and dopaminotrophic action of both GDNF and TGFβ1 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.
AB - The objective was to discern the neuroregenerative effect of grafts of extra-adrenal cells of the Zuckerkandl's paraganglion (ZP) in the nigrostriatal circuit, by using the retrograde model of parkinsonism in rats. The antiparkinsonian efficacy of two types of grafting procedures was studied (cell aggregates vs. dispersed cells), and GDNF and TGFβ1 (dopaminotrophic factors) as well as dopamine presence in extra-adrenal tissue was analyzed. Extra-adrenal chromaffin cells are noradrenergics, tissue dopamine is low, and they express both GDNF and TGFβ1. 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, and they express higher levels of GDNF. Higher survivability and GDNF content together with the neurorestorative and dopaminotrophic action of both GDNF and TGFβ1 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.
KW - Extra-adrenal
KW - GDNF
KW - Graft
KW - Parkinson
KW - Regeneration
KW - TGFβ
KW - Trophic
KW - Zuckerkandl's paraganglion
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U2 - 10.1016/j.nbd.2007.11.009
DO - 10.1016/j.nbd.2007.11.009
M3 - Article
C2 - 18206378
AN - SCOPUS:39249084874
SN - 0969-9961
VL - 29
SP - 529
EP - 542
JO - Neurobiology of Disease
JF - Neurobiology of Disease
IS - 3
ER -