RGD Reference Report - Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats. - Rat Genome Database

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

Authors: Morel, G R  Sosa, Y E  Bellini, M J  Carri, N G  Rodriguez, S S  Bohn, M C  Goya, R G 
Citation: Morel GR, etal., Neuroscience. 2010 May 19;167(3):946-53. doi: 10.1016/j.neuroscience.2010.02.053. Epub 2010 Feb 26.
RGD ID: 405878070
Pubmed: PMID:20219648   (View Abstract at PubMed)
PMCID: PMC2854198   (View Article at PubMed Central)
DOI: DOI:10.1016/j.neuroscience.2010.02.053   (Journal Full-text)

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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
GDNFHumanhyperprolactinemia treatmentISOGdnf (Rattus norvegicus) RGD 
GdnfRathyperprolactinemia treatmentIMP  RGD 
GdnfMousehyperprolactinemia treatmentISOGdnf (Rattus norvegicus) RGD 

Objects Annotated

Genes (Rattus norvegicus)
Gdnf  (glial cell derived neurotrophic factor)

Genes (Mus musculus)
Gdnf  (glial cell line derived neurotrophic factor)

Genes (Homo sapiens)
GDNF  (glial cell derived neurotrophic factor)


Additional Information