Functional regeneration in a rat Parkinson's model after intrastriatal grafts of glial cell line-derived neurotrophic factor and transforming growth factor beta1-expressing extra-adrenal chromaffin cells of the Zuckerkandl's organ.
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-beta(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-beta(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.
Espejo
E F
EF
Departamento de Fisiologia Medica y Biofisica, Universidad de Sevilla, E-41009 Sevilla, Spain. efespejo@us.es
Gonzalez-Albo
M C
MC
Moraes
J P
JP
El Banoua
F
F
Flores
J A
JA
Caraballo
I
I
D000313:Adrenal Medulla / Q000166:cytology / Q000637:transplantation; D000818:Animals; D017690:Cell Transplantation; D019439:Chromaffin Cells / Q000378:metabolism / Q000637:transplantation*; D003342:Corpus Striatum / Q000737:chemistry / Q000378:metabolism / Q000473:pathology; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism; D015870:Gene Expression; D051100:Glial Cell Line-Derived Neurotrophic Factor; D006085:Graft Survival; D009043:Motor Activity; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins / Q000032:analysis / Q000096:biosynthesis*; D016627:Oxidopamine; D010220:Para-Aortic Bodies / Q000166:cytology / Q000637:transplantation; D010302:Parkinson Disease, Secondary / Q000139:chemically induced / Q000473:pathology / Q000628:therapy*; D051381:Rats; D017208:Rats, Wistar; D020127:Recovery of Function; D012038:Regeneration / Q000502:physiology*; D013378:Substantia Nigra / Q000378:metabolism / Q000473:pathology / Q000601:surgery*; D009435:Synaptic Transmission; D016212:Transforming Growth Factor beta / Q000032:analysis / Q000096:biosynthesis*; D053773:Transforming Growth Factor beta1; D016896:Treatment Outcome
C495041:Gdnf protein, rat; D051100:Glial Cell Line-Derived Neurotrophic Factor; D009414:Nerve Growth Factors; D009419:Nerve Tissue Proteins; C508962:Tgfb1 protein, rat; D016212:Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; D016627:Oxidopamine; D004298:Dopamine