Selective Glial Cell Line-Derived Neurotrophic Factor Production in Adult Dopaminergic Carotid Body CellsIn Situand after Intrastriatal Transplantation

• DOI: 10.1523/jneurosci.4312-04.2005
• Publication Date: 2005-04-20T19:08:09Z
• Authors: Javier Villadiego; Simón Méndez-Ferrer; Teresa Valdés-Sán...; Inmaculada Silos-...; Isabel Fariñas; José López-Barneo; Juan J. Toledo-Aral
• Keywords: 0301 basic medicine; GDNF knock-out mice; Dopamine; Enzyme-Linked Immunosorbent Assay; Mice, Transgenic; parkinsonian models; glomus cells; Mice; 03 medical and health sciences; Microscopy, Electron, Transmission; Glial Fibrillary Acidic Protein; Animals; Glial Cell Line-Derived Neurotrophic Factor; Cells, Cultured; GDNF expression; Analysis of Variance; Carotid Body; Age Factors; MPTP Poisoning; Cell Differentiation; carotid body; Immunohistochemistry; Corpus Striatum; Mice, Inbred C57BL; Disease Models, Animal; intrastriatal transplants; Animals, Newborn; 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

Glial cell line-derived neurotrophic factor (GDNF) exerts a notable protective effect on dopaminergic neurons in rodent and primate models of Parkinson's disease (PD). The clinical applicability this therapy is, however, hampered by the need durable stable GDNF source allowing safe continuous delivery trophic into brain parenchyma. Intrastriatal carotid body (CB) autografting is neuroprotective potentially useful PD. It induces long-term recovery parkinsonian animals through nigrostriatal causes amelioration symptoms some PD patients. Moreover, adult CB has been shown to express GDNF. Here we show, using heterozygous GDNF/lacZ knock-out mice, that unexpectedly glomus, or type I, cells are Among neural paraneural tested, glomus those synthesize release highest amount (as measured standard situ ELISA). Furthermore, expression maintained after intrastriatal grafting aged 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated animals. Thus, appear be prototypical abundant sources GDNF, ideally suited used as biological pumps for endogenous factors other neurodegenerative diseases.