Your browser doesn't support javascript.
loading
Mostrar: 20 | 50 | 100
Resultados 1 - 1 de 1
Filtrar
Más filtros










Base de datos
Intervalo de año de publicación
1.
J Neurosci ; 29(30): 9651-9, 2009 Jul 29.
Artículo en Inglés | MEDLINE | ID: mdl-19641128

RESUMEN

Neurotrophic factors are promising candidates for the treatment of Parkinson's disease (PD). Mesencephalic astrocyte-derived neurotrophic factor (MANF) belongs to a novel evolutionarily conserved family of neurotrophic factors. We examined whether MANF has neuroprotective and neurorestorative effect in an experimental model of PD in rats. We also studied the distribution and transportation of intrastriatally injected MANF in the brain and compared it with glial cell line-derived neurotrophic factor (GDNF). Unilateral lesion of nigrostriatal dopaminergic system was induced by intrastriatal injection of 6-hydroxydopamine (6-OHDA). Amphetamine-induced turning behavior was monitored up to 12 weeks after the unilateral lesion. The local diffusion at the injection site and transportation profiles of intrastriatally injected MANF and GDNF were studied by immunohistochemical detection of the unlabeled growth factors as well as by autoradiographic and gamma counting detection of (125)I-labeled trophic factors. Intrastriatally injected MANF protected nigrostriatal dopaminergic nerves from 6-OHDA-induced degeneration as evaluated by counting tyrosine hydroxylase (TH)-positive cell bodies in the substantia nigra (SN) and TH-positive fibers in the striatum. More importantly, MANF also restored the function of the nigrostriatal dopaminergic system when administered either 6 h before or 4 weeks after 6-OHDA administration in the striatum. MANF was distributed throughout the striatum more readily than GDNF. The mechanism of MANF action differs from that of GDNF because intrastriatally injected (125)I-MANF was transported to the frontal cortex, whereas (125)I-GDNF was transported to the SN. Our results suggest that MANF is readily distributed throughout the striatum and has significant therapeutic potential for the treatment of PD.


Asunto(s)
Proteínas del Tejido Nervioso/administración & dosificación , Fármacos Neuroprotectores/administración & dosificación , Enfermedad de Parkinson Secundaria/tratamiento farmacológico , Animales , Cuerpo Estriado/efectos de los fármacos , Cuerpo Estriado/fisiopatología , Modelos Animales de Enfermedad , Dopamina/metabolismo , Factor Neurotrófico Derivado de la Línea Celular Glial/administración & dosificación , Factor Neurotrófico Derivado de la Línea Celular Glial/farmacocinética , Humanos , Masculino , Actividad Motora/efectos de los fármacos , Degeneración Nerviosa/tratamiento farmacológico , Factores de Crecimiento Nervioso , Proteínas del Tejido Nervioso/farmacocinética , Neuronas/efectos de los fármacos , Neuronas/fisiología , Fármacos Neuroprotectores/farmacocinética , Oxidopamina , Enfermedad de Parkinson Secundaria/inducido químicamente , Ratas , Ratas Wistar , Proteínas Recombinantes/administración & dosificación , Proteínas Recombinantes/farmacocinética , Sustancia Negra/efectos de los fármacos , Sustancia Negra/fisiopatología , Factores de Tiempo
SELECCIÓN DE REFERENCIAS
DETALLE DE LA BÚSQUEDA