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
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/128193
Ver los metadatos del registro completo
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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<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<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<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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Universidad Nacional de La Plata |
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SEDICI (UNLP) - Universidad Nacional de La Plata |
repository.mail.fl_str_mv |
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