Estudio de la neurogénesis adulta en modelos experimentales de enfermedad de parkinson

Resumen

Adult neurogenesis seems to be impaired in neurodegenerative diseases such as Parkinson's disease (PD). in fact, the dopaminergic denervation characteristic of PD alters the neurogenic subventricular zone (SVZ). In this area, new cells are continuously generated and migrate to the olfactory bulb (OB) to become interneurons. As dopamine plays an important role in the SVZ, we investigated the impact of nigrostriatal lesion on the cell population of OB of monkeys rendered parkinsonian by the administration of neurotoxin l-methyl-4-phenyl-l,2,3,6 tetrahydropyridine. In these animals the number of olfactory tyrosine hydroxylase-immunoreactive (TH-ir) neurons was increased up to 100% as compared to controls, but their phenotype did not change. The increased TH-ir cell population detected in the OB of parkinsonian monkeys might contribute to the hyposmia reported by PD patients.%&/In addition, the adult neurogenesis is a dynamic process that can be regulated by different factors such as neurotransmitters and trophic factors. As carotid body (CB) has been used as cellular source for cell therapy in PD because its cells express several growth factors and dopamine, we investigated the ability of intrastriatal CB grafts to stimulate the proliferation and neuronal differentiation of newborn cells in the SVZ/OB-system and striatum of parkinsonian rats grafted with CB aggregates. Glomus cells expressed TH and growth factors and were stained with 5-bromo-2¿-deoxyuridine after graft, thus indicating their ability for self-renewal. In addition, striatal CB graft did not increase cell migration in the SVZ/OB-system but increased neural progenitor proliferation in the striatum and promoted differentiation of neural progenitor cells into neurons in the OB and striatum. Taken together, our findings indicate that the striatal CB graft exerts an effect on adult neurogenesis, probably by the growth factors contained in its cells.