Document Detail


Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats.
MedLine Citation:
PMID:  20219648     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
Progressive dysfunction of hypothalamic tuberoinfundibular dopaminergic (TIDA) neurons during normal aging is associated in the female rat with chronic hyperprolactinemia. We assessed the effectiveness of glial cell line-derived neurotrophic factor (GDNF) gene therapy to restore TIDA neuron function in senile female rats and reverse their chronic hyperprolactinemia. Young (2.5 months) and senile (29 months) rats received a bilateral intrahypothalamic injection (10(10) pfu) of either an adenoviral vector expressing the gene for beta-galactosidase; (Y-betagal and S-betagal, respectively) or a vector expressing rat GDNF (Y-GDNF and S-GDNF, respectively). Transgenic GDNF levels in supernatants of GDNF adenovector-transduced N2a neuronal cell cultures were 25+/-4 ng/ml, as determined by bioassay. In the rats, serum prolactin (PRL) was measured at regular intervals. On day 17 animals were sacrificed and neuronal nuclear antigen (NeuN) and tyrosine hydroxylase (TH) immunoreactive cells counted in the arcuate-periventricular hypothalamic region. The S-GDNF but not the S-betagal rats, showed a significant reduction in body weight. The chronic hyperprolactinemia of the senile females was significantly ameliorated in the S-GDNF rats (P<0.05) but not in the S-betagal rats. Neither age nor GDNF induced significant changes in the number of NeuN and TH neurons. We conclude that transgenic GDNF ameliorates chronic hyperprolactinemia in aging female rats, probably by restoring TIDA neuron function.
Authors:
G R Morel; Y E Sosa; M J Bellini; N G Carri; S S Rodriguez; M C Bohn; R G Goya
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Publication Detail:
Type:  Journal Article; Research Support, N.I.H., Extramural; Research Support, Non-U.S. Gov't     Date:  2010-02-26
Journal Detail:
Title:  Neuroscience     Volume:  167     ISSN:  1873-7544     ISO Abbreviation:  Neuroscience     Publication Date:  2010 May 
Date Detail:
Created Date:  2010-04-13     Completed Date:  2010-06-29     Revised Date:  2014-09-10    
Medline Journal Info:
Nlm Unique ID:  7605074     Medline TA:  Neuroscience     Country:  United States    
Other Details:
Languages:  eng     Pagination:  946-53     Citation Subset:  IM    
Copyright Information:
Copyright 2010 IBRO. Published by Elsevier Ltd. All rights reserved.
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MeSH Terms
Descriptor/Qualifier:
Adenoviridae / genetics
Aging / metabolism*
Animals
Antigens, Nuclear / metabolism
Arcuate Nucleus / cytology,  metabolism
Cell Count
Cells, Cultured
Chronic Disease / therapy
Female
Genes, Reporter / genetics
Genetic Therapy / methods*
Genetic Vectors / genetics,  pharmacology
Glial Cell Line-Derived Neurotrophic Factor / genetics*
Hyperprolactinemia / genetics*,  metabolism,  therapy*
Lactotrophs / metabolism,  secretion
Microinjections / methods
Nerve Tissue Proteins / metabolism
Neurons / cytology,  metabolism
Prolactin / analysis,  blood,  secretion
Rats
Rats, Sprague-Dawley
Recovery of Function / genetics
Treatment Outcome
Tuber Cinereum / metabolism,  physiopathology,  secretion
Tyrosine 3-Monooxygenase / metabolism
beta-Galactosidase / genetics
Grant Support
ID/Acronym/Agency:
R01 AG029798/AG/NIA NIH HHS; R01 AG029798-02/AG/NIA NIH HHS; R01AG029798-2/AG/NIA NIH HHS
Chemical
Reg. No./Substance:
0/Antigens, Nuclear; 0/Glial Cell Line-Derived Neurotrophic Factor; 0/Nerve Tissue Proteins; 0/NeuN protein, rat; 9002-62-4/Prolactin; EC 1.14.16.2/Tyrosine 3-Monooxygenase; EC 3.2.1.23/beta-Galactosidase
Comments/Corrections

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