INIBIOLP   05426
INSTITUTO DE INVESTIGACIONES BIOQUIMICAS DE LA PLATA "PROF. DR. RODOLFO R. BRENNER"
Unidad Ejecutora - UE
artículos
Título:
Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats
Autor/es:
MOREL GR; SOSA YE; BELLINI MJ; CARRI, NG; RODRIGUEZ SS; BOHN MARTHA C; GOYA RG
Revista:
NEUROSCIENCE
Editorial:
PERGAMON-ELSEVIER SCIENCE LTD
Referencias:
Año: 2010 vol. 167 p. 946 - 953
ISSN:
0306-4522
Resumen:
AbstractProgressive 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 (1010 pfu) of either an adenoviral vector expressing
the gene for -galactosidase; (Y-gal and S-gal, 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 254 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 arcuateperiventricular hypothalamic region.
The S-GDNF but not the S-gal rats, showed a significant
reduction in body weight. The chronic hyperprolactinemia of
the senile females was significantly ameliorated in the SGDNF
rats (P<0.05) but not in the S-gal 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 functionP<0.05) but not in the S-10 pfu) of either an adenoviral vector expressing
the gene for -galactosidase; (Y-gal and S-gal, 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 254 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 arcuateperiventricular hypothalamic region.
The S-GDNF but not the S-gal rats, showed a significant
reduction in body weight. The chronic hyperprolactinemia of
the senile females was significantly ameliorated in the SGDNF
rats (P<0.05) but not in the S-gal 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 functionP<0.05) but not in the S--galactosidase; (Y-gal and S-gal, 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 254 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 arcuateperiventricular hypothalamic region.
The S-GDNF but not the S-gal rats, showed a significant
reduction in body weight. The chronic hyperprolactinemia of
the senile females was significantly ameliorated in the SGDNF
rats (P<0.05) but not in the S-gal 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 functionP<0.05) but not in the S-gal rats, showed a significant
reduction in body weight. The chronic hyperprolactinemia of
the senile females was significantly ameliorated in the SGDNF
rats (P<0.05) but not in the S-gal 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 functionP<0.05) but not in the S-gal 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