title: Neuroprotective and reparative effects of carotid body grafts in a chronic MPTP model of Parkinson's disease.
abstract: Intrastriatal transplantation of dopaminergic carotid body (CB) cells ameliorates parkinsonism in animal models and, with less efficacy, in Parkinson's disease patients. CB-based cell therapy was initially proposed because of its high dopamine content. However, later studies suggested that its beneficial effect might be due to a trophic action exerted on nigrostriatal neurons. Compatible with this concept are the high levels of neurotrophic factors encountered in CB cells. To test experimentally this idea, unilateral striatal transplants were performed with a sham graft in the contralateral striatum, as a robust internal control. Thereafter, the dopaminergic neurotoxin 1-methyl-4-phenyl-1,2,3,6, -tetrahydropyridine was injected during 3 months. CB grafts protected from degeneration ipsilateral nigral dopaminergic neurons projecting to the transplant in a dose-dependent manner regarding size and glial cell line-derived neurotrophic factor expression. Grafts performed at different times after the onset of the neurotoxic treatment demonstrated with histological and behavioral methods protection and repair of the nigrostriatal pathway by CB transplants. This study provides a mechanistic explanation for the action of CB transplants on parkinsonian models. It should also help to improve cell therapy approaches to Parkinson's disease.
authors: Instituto de Biomedicina de Sevilla-IBiS, HUVR/Universidad de Sevilla/CSIC, Seville, Spain.
authors: Ana B
authors: AB
authors: Muñoz-Manchado
authors: Javier
authors: J
authors: Villadiego
authors: Nela
authors: N
authors: Suárez-Luna
authors: Alfonso
authors: A
authors: Bermejo-Navas
authors: Pablo
authors: P
authors: Garrido-Gil
authors: José L
authors: JL
authors: Labandeira-García
authors: Miriam
authors: M
authors: Echevarría
authors: José
authors: J
authors: López-Barneo
authors: Juan J
authors: JJ
authors: Toledo-Aral
mesh_terms: D000818:Animals; D002344:Carotid Body / Q000166:cytology / Q000637:transplantation; D003342:Corpus Striatum / Q000378:metabolism; D004195:Disease Models, Animal; D059290:Dopaminergic Neurons / Q000378:metabolism / Q000637:transplantation*; D051100:Glial Cell Line-Derived Neurotrophic Factor / Q000235:genetics / Q000378:metabolism; D051379:Mice; D008810:Mice, Inbred C57BL; D020734:Parkinsonian Disorders / Q000378:metabolism / Q000601:surgery; D012333:RNA, Messenger / Q000032:analysis*; D060888:Real-Time Polymerase Chain Reaction
chemical_list: D051100:Glial Cell Line-Derived Neurotrophic Factor; D012333:RNA, Messenger