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

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 funct...

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Detalles Bibliográficos
Autores principales: Morel, Gustavo Ramón, Sosa, Yolanda Elena, Bellini, María José, Carri, Néstor Gabriel, Rodríguez, Silvia Susana, Bohn, Martha C., Goya, Rodolfo Gustavo
Formato: Articulo
Lenguaje:Inglés
Publicado: 2010
Materias:
Acceso en línea:http://sedici.unlp.edu.ar/handle/10915/128193
Aporte de:
id I19-R120-10915-128193
record_format dspace
institution Universidad Nacional de La Plata
institution_str I-19
repository_str R-120
collection SEDICI (UNLP)
language Inglés
topic Biología
Aging
DA neurodegeneration
TIDA neurons
chronic hyperprolactinemia
GDNF
gene therapy
spellingShingle Biología
Aging
DA neurodegeneration
TIDA neurons
chronic hyperprolactinemia
GDNF
gene therapy
Morel, Gustavo Ramón
Sosa, Yolanda Elena
Bellini, María José
Carri, Néstor Gabriel
Rodríguez, Silvia Susana
Bohn, Martha C.
Goya, Rodolfo Gustavo
Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
topic_facet Biología
Aging
DA neurodegeneration
TIDA neurons
chronic hyperprolactinemia
GDNF
gene therapy
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.
format Articulo
Articulo
author Morel, Gustavo Ramón
Sosa, Yolanda Elena
Bellini, María José
Carri, Néstor Gabriel
Rodríguez, Silvia Susana
Bohn, Martha C.
Goya, Rodolfo Gustavo
author_facet Morel, Gustavo Ramón
Sosa, Yolanda Elena
Bellini, María José
Carri, Néstor Gabriel
Rodríguez, Silvia Susana
Bohn, Martha C.
Goya, Rodolfo Gustavo
author_sort Morel, Gustavo Ramón
title Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
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
publishDate 2010
url http://sedici.unlp.edu.ar/handle/10915/128193
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