Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats

Autores
Morel, Gustavo Ramón; Sosa, Yolanda Elena; Bellini, María José; Carri, Néstor Gabriel; Rodríguez, Silvia Susana; Bohn, Martha C.; Goya, Rodolfo Gustavo
Año de publicación
2010
Idioma
inglés
Tipo de recurso
artículo
Estado
versión publicada
Descripción
Progressive dysfunction of hypothalamic tu-beroinfundibular dopaminergic (TIDA) neurons during nor-mal aging is associated in the female rat with chronic hyper-prolactinemia. We assessed the effectiveness of glial cellline-derived neurotrophic factor (GDNF) gene therapy to re-store TIDA neuron function in senile female rats and reversetheir chronic hyperprolactinemia. Young (2.5 months) andsenile (29 months) rats received a bilateral intrahypothalamicinjection (1010pfu) of either an adenoviral vector expressingthe gene for β-galactosidase; (Y-βgal and S-βgal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF,respectively). Transgenic GDNF levels in supernatants ofGDNF adenovector-transduced N2a neuronal cell cultureswere 25±4 ng/ml, as determined by bioassay. In the rats,serum prolactin (PRL) was measured at regular intervals. Onday 17 animals were sacrificed and neuronal nuclear antigen(NeuN) and tyrosine hydroxylase (TH) immunoreactive cellscounted in the arcuate–periventricular hypothalamic region.The S-GDNF but not the S-βgal rats, showed a significantreduction in body weight. The chronic hyperprolactinemia ofthe senile females was significantly ameliorated in the S-GDNF rats (P<0.05) but not in the S-βgal rats. Neither age norGDNF induced significant changes in the number of NeuNand TH neurons. We conclude that transgenic GDNF amelio-rates chronic hyperprolactinemia in aging female rats, prob-ably by restoring TIDA neuron function.
Instituto Multidisciplinario de Biología Celular
Instituto de Investigaciones Bioquímicas de La Plata
Materia
Biología
Aging
DA neurodegeneration
TIDA neurons
chronic hyperprolactinemia
GDNF
gene therapy
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:10915/128193

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repository_id_str 1329
network_name_str SEDICI (UNLP)
spelling Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile ratsMorel, Gustavo RamónSosa, Yolanda ElenaBellini, María JoséCarri, Néstor GabrielRodríguez, Silvia SusanaBohn, Martha C.Goya, Rodolfo GustavoBiologíaAgingDA neurodegenerationTIDA neuronschronic hyperprolactinemiaGDNFgene therapyProgressive dysfunction of hypothalamic tu-beroinfundibular dopaminergic (TIDA) neurons during nor-mal aging is associated in the female rat with chronic hyper-prolactinemia. We assessed the effectiveness of glial cellline-derived neurotrophic factor (GDNF) gene therapy to re-store TIDA neuron function in senile female rats and reversetheir chronic hyperprolactinemia. Young (2.5 months) andsenile (29 months) rats received a bilateral intrahypothalamicinjection (1010pfu) of either an adenoviral vector expressingthe gene for β-galactosidase; (Y-βgal and S-βgal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF,respectively). Transgenic GDNF levels in supernatants ofGDNF adenovector-transduced N2a neuronal cell cultureswere 25±4 ng/ml, as determined by bioassay. In the rats,serum prolactin (PRL) was measured at regular intervals. Onday 17 animals were sacrificed and neuronal nuclear antigen(NeuN) and tyrosine hydroxylase (TH) immunoreactive cellscounted in the arcuate–periventricular hypothalamic region.The S-GDNF but not the S-βgal rats, showed a significantreduction in body weight. The chronic hyperprolactinemia ofthe senile females was significantly ameliorated in the S-GDNF rats (P&lt;0.05) but not in the S-βgal rats. Neither age norGDNF induced significant changes in the number of NeuNand TH neurons. We conclude that transgenic GDNF amelio-rates chronic hyperprolactinemia in aging female rats, prob-ably by restoring TIDA neuron function.Instituto Multidisciplinario de Biología CelularInstituto de Investigaciones Bioquímicas de La Plata2010-02-26info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf946-953http://sedici.unlp.edu.ar/handle/10915/128193enginfo:eu-repo/semantics/altIdentifier/issn/1873-7544info:eu-repo/semantics/altIdentifier/issn/0306-4522info:eu-repo/semantics/altIdentifier/pmid/20219648info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuroscience.2010.02.053info: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:UNLP2025-09-29T11:30:58Zoai:sedici.unlp.edu.ar:10915/128193Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:30:59.079SEDICI (UNLP) - Universidad Nacional de La Platafalse
dc.title.none.fl_str_mv Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
title Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
spellingShingle Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
Morel, Gustavo Ramón
Biología
Aging
DA neurodegeneration
TIDA neurons
chronic hyperprolactinemia
GDNF
gene therapy
title_short Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
title_full Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
title_fullStr Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
title_full_unstemmed Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
title_sort Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
dc.creator.none.fl_str_mv Morel, Gustavo Ramón
Sosa, Yolanda Elena
Bellini, María José
Carri, Néstor Gabriel
Rodríguez, Silvia Susana
Bohn, Martha C.
Goya, Rodolfo Gustavo
author Morel, Gustavo Ramón
author_facet Morel, Gustavo Ramón
Sosa, Yolanda Elena
Bellini, María José
Carri, Néstor Gabriel
Rodríguez, Silvia Susana
Bohn, Martha C.
Goya, Rodolfo Gustavo
author_role author
author2 Sosa, Yolanda Elena
Bellini, María José
Carri, Néstor Gabriel
Rodríguez, Silvia Susana
Bohn, Martha C.
Goya, Rodolfo Gustavo
author2_role author
author
author
author
author
author
dc.subject.none.fl_str_mv Biología
Aging
DA neurodegeneration
TIDA neurons
chronic hyperprolactinemia
GDNF
gene therapy
topic Biología
Aging
DA neurodegeneration
TIDA neurons
chronic hyperprolactinemia
GDNF
gene therapy
dc.description.none.fl_txt_mv Progressive dysfunction of hypothalamic tu-beroinfundibular dopaminergic (TIDA) neurons during nor-mal aging is associated in the female rat with chronic hyper-prolactinemia. We assessed the effectiveness of glial cellline-derived neurotrophic factor (GDNF) gene therapy to re-store TIDA neuron function in senile female rats and reversetheir chronic hyperprolactinemia. Young (2.5 months) andsenile (29 months) rats received a bilateral intrahypothalamicinjection (1010pfu) of either an adenoviral vector expressingthe gene for β-galactosidase; (Y-βgal and S-βgal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF,respectively). Transgenic GDNF levels in supernatants ofGDNF adenovector-transduced N2a neuronal cell cultureswere 25±4 ng/ml, as determined by bioassay. In the rats,serum prolactin (PRL) was measured at regular intervals. Onday 17 animals were sacrificed and neuronal nuclear antigen(NeuN) and tyrosine hydroxylase (TH) immunoreactive cellscounted in the arcuate–periventricular hypothalamic region.The S-GDNF but not the S-βgal rats, showed a significantreduction in body weight. The chronic hyperprolactinemia ofthe senile females was significantly ameliorated in the S-GDNF rats (P&lt;0.05) but not in the S-βgal rats. Neither age norGDNF induced significant changes in the number of NeuNand TH neurons. We conclude that transgenic GDNF amelio-rates chronic hyperprolactinemia in aging female rats, prob-ably by restoring TIDA neuron function.
Instituto Multidisciplinario de Biología Celular
Instituto de Investigaciones Bioquímicas de La Plata
description Progressive dysfunction of hypothalamic tu-beroinfundibular dopaminergic (TIDA) neurons during nor-mal aging is associated in the female rat with chronic hyper-prolactinemia. We assessed the effectiveness of glial cellline-derived neurotrophic factor (GDNF) gene therapy to re-store TIDA neuron function in senile female rats and reversetheir chronic hyperprolactinemia. Young (2.5 months) andsenile (29 months) rats received a bilateral intrahypothalamicinjection (1010pfu) of either an adenoviral vector expressingthe gene for β-galactosidase; (Y-βgal and S-βgal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF,respectively). Transgenic GDNF levels in supernatants ofGDNF adenovector-transduced N2a neuronal cell cultureswere 25±4 ng/ml, as determined by bioassay. In the rats,serum prolactin (PRL) was measured at regular intervals. Onday 17 animals were sacrificed and neuronal nuclear antigen(NeuN) and tyrosine hydroxylase (TH) immunoreactive cellscounted in the arcuate–periventricular hypothalamic region.The S-GDNF but not the S-βgal rats, showed a significantreduction in body weight. The chronic hyperprolactinemia ofthe senile females was significantly ameliorated in the S-GDNF rats (P&lt;0.05) but not in the S-βgal rats. Neither age norGDNF induced significant changes in the number of NeuNand TH neurons. We conclude that transgenic GDNF amelio-rates chronic hyperprolactinemia in aging female rats, prob-ably by restoring TIDA neuron function.
publishDate 2010
dc.date.none.fl_str_mv 2010-02-26
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/10915/128193
url http://sedici.unlp.edu.ar/handle/10915/128193
dc.language.none.fl_str_mv eng
language eng
dc.relation.none.fl_str_mv info:eu-repo/semantics/altIdentifier/issn/1873-7544
info:eu-repo/semantics/altIdentifier/issn/0306-4522
info:eu-repo/semantics/altIdentifier/pmid/20219648
info:eu-repo/semantics/altIdentifier/doi/10.1016/j.neuroscience.2010.02.053
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
946-953
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instname_str Universidad Nacional de La Plata
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repository.name.fl_str_mv SEDICI (UNLP) - Universidad Nacional de La Plata
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