Dopaminergic cells of the carotid body: physiological significance and possible therapeutic applications in Parkinson's disease.
Parkinson's disease is a neurodegenerative disorder characterized by the progressive loss of dopaminergic neurons in the substantia nigra projecting to the striatum. One therapeutic approach to this disease has been the intrastriatal transplantation of dopamine-secreting cells. We have investigated the suitability of glomus cells of the carotid body for dopamine-cell replacement in animal models of Parkinson's disease. Carotid body glomus cells are physiologic arterial oxygen sensors that release large amounts of dopamine in response to hypoxia. We have used hemi-Parkinsonian rats, induced by injection of 6-hydroxydopamine into the substantia nigra, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine treated monkeys with chronic Parkinsonism. In both cases we made transplants of carotid body cell aggregates into the putamen. Functional recovery of the grafted animals was observed after the surgery and was stable for several months. Although the study was more detailed in the rat, in the two animal models the amelioration of the motor deficits was paralleled by striatal dopaminergic reinnervation and survival of grafted glomus cells. Our results suggest that intrastriatal autotransplants of carotid body tissue could be a feasible technique to treat some cases of Parkinson's disease in humans.
Toledo-Aral
Juan José
JJ
Laboratorio de Investigaciones Biomédicas, Departamento de Fisiología and Hospital Universitario Virgen del Rocío, Universidad de Sevilla, Seville, Spain.
Méndez-Ferrer
Simón
S
Pardal
Ricardo
R
López-Barneo
José
J
D000818:Animals; D016380:Brain Tissue Transplantation / Q000379:methods* / Q000639:trends; D002344:Carotid Body / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D004195:Disease Models, Animal; D004298:Dopamine / Q000378:metabolism*; D006085:Graft Survival / Q000502:physiology; D006801:Humans; D000860:Hypoxia / Q000378:metabolism / Q000503:physiopathology; D017072:Neostriatum / Q000378:metabolism / Q000503:physiopathology / Q000601:surgery*; D009414:Nerve Growth Factors / Q000378:metabolism; D009474:Neurons / Q000166:cytology* / Q000378:metabolism / Q000637:transplantation*; D020734:Parkinsonian Disorders / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy*; D051381:Rats; D020127:Recovery of Function / Q000502:physiology
D009414:Nerve Growth Factors; D004298:Dopamine