Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction

Autores
Hereñú, Claudia Beatriz; Cristina, Silvia Carolina; Rimoldi, Omar Jorge; Becú de Villalobos, Damasia; Cambiaggi, Vanina Laura; Portiansky, Enrique Leo; Goya, Rodolfo Gustavo
Año de publicación
2007
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
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 × 109 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
Materia
Ciencias Médicas
Ciencias Veterinarias
aging
DA neurodegeneration
TIDA neurons
hyperprolactinemia
IGF-I
Nivel de accesibilidad
acceso abierto
Condiciones de uso
http://creativecommons.org/licenses/by-nc-sa/4.0/
Repositorio
SEDICI (UNLP)
Institución
Universidad Nacional de La Plata
OAI Identificador
oai:sedici.unlp.edu.ar:10915/82997

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network_name_str SEDICI (UNLP)
spelling Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunctionHereñú, Claudia BeatrizCristina, Silvia CarolinaRimoldi, Omar JorgeBecú de Villalobos, DamasiaCambiaggi, Vanina LauraPortiansky, Enrique LeoGoya, Rodolfo GustavoCiencias MédicasCiencias VeterinariasagingDA neurodegenerationTIDA neuronshyperprolactinemiaIGF-IInsulin-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 PlataFacultad de Ciencias MédicasFacultad de Ciencias VeterinariasFacultad de Ciencias Exactas2007info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf237-245http://sedici.unlp.edu.ar/handle/10915/82997enginfo:eu-repo/semantics/altIdentifier/issn/0969-7128info:eu-repo/semantics/altIdentifier/doi/10.1038/sj.gt.3302870info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by-nc-sa/4.0/Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:15:45Zoai:sedici.unlp.edu.ar:10915/82997Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:15:45.878SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
title Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
spellingShingle Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
Hereñú, Claudia Beatriz
Ciencias Médicas
Ciencias Veterinarias
aging
DA neurodegeneration
TIDA neurons
hyperprolactinemia
IGF-I
title_short Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
title_full Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
title_fullStr Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
title_full_unstemmed Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
title_sort Restorative effect of insulin-like growth factor-I gene therapy in the hypothalamus of senile rats with dopaminergic dysfunction
dc.creator.none.fl_str_mv Hereñú, Claudia Beatriz
Cristina, Silvia Carolina
Rimoldi, Omar Jorge
Becú de Villalobos, Damasia
Cambiaggi, Vanina Laura
Portiansky, Enrique Leo
Goya, Rodolfo Gustavo
author Hereñú, Claudia Beatriz
author_facet Hereñú, Claudia Beatriz
Cristina, Silvia Carolina
Rimoldi, Omar Jorge
Becú de Villalobos, Damasia
Cambiaggi, Vanina Laura
Portiansky, Enrique Leo
Goya, Rodolfo Gustavo
author_role author
author2 Cristina, Silvia Carolina
Rimoldi, Omar Jorge
Becú de Villalobos, Damasia
Cambiaggi, Vanina Laura
Portiansky, Enrique Leo
Goya, Rodolfo Gustavo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Ciencias Médicas
Ciencias Veterinarias
aging
DA neurodegeneration
TIDA neurons
hyperprolactinemia
IGF-I
topic Ciencias Médicas
Ciencias Veterinarias
aging
DA neurodegeneration
TIDA neurons
hyperprolactinemia
IGF-I
dc.description.none.fl_txt_mv 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
description 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.
publishDate 2007
dc.date.none.fl_str_mv 2007
dc.type.none.fl_str_mv info:eu-repo/semantics/article
info:eu-repo/semantics/publishedVersion
Articulo
http://purl.org/coar/resource_type/c_6501
info:ar-repo/semantics/articulo
format article
status_str publishedVersion
dc.identifier.none.fl_str_mv http://sedici.unlp.edu.ar/handle/10915/82997
url http://sedici.unlp.edu.ar/handle/10915/82997
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/0969-7128
info:eu-repo/semantics/altIdentifier/doi/10.1038/sj.gt.3302870
dc.rights.none.fl_str_mv info:eu-repo/semantics/openAccess
http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
eu_rights_str_mv openAccess
rights_invalid_str_mv http://creativecommons.org/licenses/by-nc-sa/4.0/
Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International (CC BY-NC-SA 4.0)
dc.format.none.fl_str_mv application/pdf
237-245
dc.source.none.fl_str_mv reponame:SEDICI (UNLP)
instname:Universidad Nacional de La Plata
instacron:UNLP
reponame_str SEDICI (UNLP)
collection SEDICI (UNLP)
instname_str Universidad Nacional de La Plata
instacron_str UNLP
institution UNLP
repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
repository.mail.fl_str_mv alira@sedici.unlp.edu.ar
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