REJUVENATING EFFECT OF LONG-TERM IGF-I GENE THERAPY IN THE HYPOTHALAMUS OF AGED RATS WITH DOPAMINERGIC DYSFUNCTION

LOPEZ-LEON, MICAELA; MOREL, GUSTAVO RAMON; SCHWERDT, JOSE IGNACIO; BROWN, OSCAR ALFEDO; GOYA, RODOLFO GUSTAVO; CONSOLE, GLORIA MIRIAM; SPINEDI, EDUARDO

REJUVENATION RESEARCH

MARY ANN LIEBERT INC

Lugar: New York; Año: 2017

1549-1684

The aging female rat constitutes an interesting model of spontaneous and progressive age-related dopaminergic dysfunction as it allows assessing new therapeutic strategies for Parkinson´s disease. 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 helper-dependent recombinant adenoviral vector (HDRAd-IGFI) harboring the gene for rat IGF-I. This was used it to implement long-term IGF-I gene therapy in the hypothalamus of aged female rats, which display hypothalamic dopaminergic (DA) dysfunction and as a consequence, chronic hyperprolactinemia. Rejuvenating long-term IGF-I gene therapy was implemented in young (3 mo.) and aged (24 mo.) female rats, which received a single intrahypothalamic injection of 4 X109 viral particles of either HD-RAd-IGFI or HD-RAd-DsRed (control vector) and were sacrificed 119 days post-injection. In the young animals, neither vector modified serum prolactin (PRL) levels but in the RAd-IGFI-injected aged 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 aged animals (5,874 ± 486 and 3,390 ± 498, respectively). Our results indicate that IGF-I gene therapy in aged female rats is highly effective in rejuvenating the hypothalamic DA neuron groups.