Articulo
Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
Autor
Hereñú, Claudia Beatriz
Cristina, Silvia Carolina
Rimoldi, Omar Jorge
Becú de Villalobos, Damasia
Cambiaggi, Vanina Laura
Portiansky, Enrique Leo
Goya, Rodolfo Gustavo
Institución
Resumen
Insulin-like growth factor-I (IGF-I) is emerging as a powerful neuroprotective molecule that is strongly induced in the central nervous system after different insults. We constructed a recombinant adenoviral vector (RAd-IGFI) harboring the gene for rat IGF-I and used it to implement IGF-I gene therapy in the hypothalamus of senile female rats, which display hypothalamic dopaminergic (DA) neurodegeneration and as a consequence, chronic hyperprolactinemia. Restorative IGF-I gene therapy was implemented in young (5 months) and senile (28 months) female rats, which received a single intrahypothalamic injection of 3 × 10<SUP>9</SUP> plaque-forming units of RAd-βgal (a control adenoviral vector expressing β-galactosidase) or RAd-IGFI and were killed 17 days post-injection. In the young animals, neither vector modified serum prolactin levels, but in the RAd-IGFI-injected senile rats a nearly full reversion of their hyperprolactinemic status was recorded. Morphometric analysis revealed a significant increase in the total number of tyrosine hydroxylase-positive cells in the hypothalamus of experimental as compared with control senile animals (5874±486 and 3390±498, respectively). Our results indicate that IGF-I gene therapy in senile female rats is highly effective for restoring their hypothalamic DA dysfunction and thus reversing their chronic hyperprolactinemia. Instituto de Investigaciones Bioquímicas de La Plata Facultad de Ciencias Médicas Facultad de Ciencias Veterinarias Facultad de Ciencias Exactas