Artículo
Rejuvenating Effect of Long-Term Insulin-Like Growth Factor-I Gene Therapy in the Hypothalamus of Aged Rats with Dopaminergic Dysfunction
Schwerdt, José Ignacio
; López León, Micaela
; Console de Avegliano, Gloria Miriam; Brown, Oscar Alfredo
; Morel, Gustavo Ramón
; Spinedi, Eduardo Julio
; Goya, Rodolfo Gustavo
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Fecha de publicación:
04/2018
Editorial:
Mary Ann Liebert
Revista:
Rejuvenation Research
ISSN:
1549-1684
Idioma:
Inglés
Tipo de recurso:
Artículo publicado
Clasificación temática:
Resumen
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, 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 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 months) and aged (24 months) female rats, which received a single intrahypothalamic injection of 4 × 109 viral particles of either HD-RAd-IGFI or HD-RAd-DsRed (control vector) and were sacrificed 119 days postinjection. 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 compared with control aged animals (5874 ± 486 and 3390 ± 498, respectively). Our results indicate that IGF-I gene therapy in aged female rats is highly effective in rejuvenating the hypothalamic DA neuron groups.
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Articulos(CENEXA)
Articulos de CENTRO DE ENDOCRINOLOGIA EXP.Y APLICADA (I)
Articulos de CENTRO DE ENDOCRINOLOGIA EXP.Y APLICADA (I)
Articulos(INIBIOLP)
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Articulos de INST.DE INVEST.BIOQUIMICAS DE LA PLATA
Citación
Schwerdt, José Ignacio; López León, Micaela; Console de Avegliano, Gloria Miriam; Brown, Oscar Alfredo; Morel, Gustavo Ramón; et al.; Rejuvenating Effect of Long-Term Insulin-Like Growth Factor-I Gene Therapy in the Hypothalamus of Aged Rats with Dopaminergic Dysfunction; Mary Ann Liebert; Rejuvenation Research; 21; 2; 4-2018; 102-108
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