Restorative effect of Insulin-like Growth Factor-I Gene Therapy in the Hypothalamus of senile rats with Dopaminergic dysfunction

HEREÑU CB; CRISTINA C; RIMOLDI O; BECÚ-VILLALOBOS D; CAMBIAGGI V; PORTIANSKY E; GOYA R.

GENE THERAPY

Nature Publishing Group

Año: 2006 p. 1 - 31

0969-7128

SUMMARY-Hereñú - Gene Therapy 2006 Insulin-like growth factor I (IGF-I) is emerging as a powerful neuroprotective molecule which 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 mo.) and senile (28 mo.) female rats, which received a single intrahypothalamic injection of 3 X109 plaque forming units (pfu) of RAd-βgal (a control adenoviral vector expressing $-galactosidase) or RAd-IGFI and were sacrificed 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 (TH) positive cells in the hypothalamus of experimental as compared with control senile animals (5,874 ± 486 and 3,390 ± 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.