Rejuvenating effect of long-term IGF-I gene therapy in the hypothalamus of senile rats with dopaminergic dynfunction

SCHWERDT JI; LOPEZ-LEÓN M; CONSOLE GM; BROWN OA; MOREL GR; SPINEDI E; GOYA RG

REJUVENATION RESEARCH

MARY ANN LIEBERT INC

Lugar: New York; Año: 2018

1549-1684

The aging female rat constitutes an interesting model of spontaneousand progressive age-related dopaminergic dysfunction as it allows assessing newtherapeutic 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 afterdifferent insults. We constructed a helper-dependent recombinant adenoviralvector (HDRAd-IGFI) harboring the gene for rat IGF-I and used it to implement long-termIGF-I gene therapy in the hypothalamus of senile female rats, which displayhypothalamic dopaminergic (DA) dysfunction and as a consequence, chronichyperprolactinemia. Rejuvenating long-term IGF-I gene therapy was implementedin young (3 mo.) and senile (24 mo.) female rats, which received a singleintrahypothalamic injection of 4 X109 viral particles of eitherHD-RAd-IGFIor HD-RAd-DsRed(control vector) andwere sacrificed 119 days post-injection. In the young animals, neither vectormodified serum prolactin (PRL) levels but in the RAd-IGFI-injected senile ratsa nearly full reversion of their hyperprolactinemic status was recorded.Morphometric analysis revealed a significant increase in the total number oftyrosine hydroxylase (TH) positive cells in the hypothalamus of experimental ascompared with control senile animals (5,874 ± 486 and 3,390 ± 498,respectively).  Our results indicate thatIGF-I gene therapy in senile female rats is highlyeffective for rejuvenating their hypothalamic DA dysfunction.