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

G. R. Morel; Y. E. Sosa; M. J. Bellini; N. G. Carri; S. S. Rodriguez; M. C. Bohn; R. G. Goya

doi:10.1016/j.neuroscience.2010.02.053

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

G. R. Morel, Y. E. Sosa, M. J. Bellini, N. G. Carri, S. S. Rodriguez, M. C. Bohn, R. G. Goya^*

^*Corresponding author for this work

Pediatrics

Research output: Contribution to journal › Article › peer-review

9 Scopus citations

Abstract

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 (10¹⁰ pfu) of either an adenoviral vector expressing the 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 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-βgal 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-βgal 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.

Original language	English (US)
Pages (from-to)	946-953
Number of pages	8
Journal	Neuroscience
Volume	167
Issue number	3
DOIs	https://doi.org/10.1016/j.neuroscience.2010.02.053
State	Published - May 2010

Keywords

Aging
Chronic hyperprolactinemia
DA neurodegeneration
GDNF
Gene therapy
TIDA neurons

ASJC Scopus subject areas

Neuroscience(all)

Access to Document

10.1016/j.neuroscience.2010.02.053

Cite this

@article{fe7085d9ae174e9581fb9977abb7c13b,

title = "Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats",

abstract = "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 (1010 pfu) of either an adenoviral vector expressing the 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 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-βgal 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-βgal 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.",

keywords = "Aging, Chronic hyperprolactinemia, DA neurodegeneration, GDNF, Gene therapy, TIDA neurons",

author = "Morel, {G. R.} and Sosa, {Y. E.} and Bellini, {M. J.} and Carri, {N. G.} and Rodriguez, {S. S.} and Bohn, {M. C.} and Goya, {R. G.}",

note = "Funding Information: This study was supported in part by a Luis Santalo grant from the Argentine Research Council (CONICET) , grant# PICT38214 from the (Argentine) National Agency for the Promotion of Science and Technology and NIH grant R01AG029798-2 from the National Institute on Aging (NIA) and the Fogarty International Center (FIC) to RGG and MCB. RGG and NGC are Research Career scientists of CONICET.",

year = "2010",

month = may,

doi = "10.1016/j.neuroscience.2010.02.053",

language = "English (US)",

volume = "167",

pages = "946--953",

journal = "Neuroscience",

issn = "0306-4522",

publisher = "Elsevier Limited",

number = "3",

}

TY - JOUR

T1 - Glial cell line-derived neurotrophic factor gene therapy ameliorates chronic hyperprolactinemia in senile rats

AU - Morel, G. R.

AU - Sosa, Y. E.

AU - Bellini, M. J.

AU - Carri, N. G.

AU - Rodriguez, S. S.

AU - Bohn, M. C.

AU - Goya, R. G.

N1 - Funding Information: This study was supported in part by a Luis Santalo grant from the Argentine Research Council (CONICET) , grant# PICT38214 from the (Argentine) National Agency for the Promotion of Science and Technology and NIH grant R01AG029798-2 from the National Institute on Aging (NIA) and the Fogarty International Center (FIC) to RGG and MCB. RGG and NGC are Research Career scientists of CONICET.

PY - 2010/5

Y1 - 2010/5

N2 - 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 (1010 pfu) of either an adenoviral vector expressing the 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 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-βgal 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-βgal 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.

AB - 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 (1010 pfu) of either an adenoviral vector expressing the 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 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-βgal 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-βgal 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.

KW - Aging

KW - Chronic hyperprolactinemia

KW - DA neurodegeneration

KW - GDNF

KW - Gene therapy

KW - TIDA neurons

UR - http://www.scopus.com/inward/record.url?scp=77951268235&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951268235&partnerID=8YFLogxK

U2 - 10.1016/j.neuroscience.2010.02.053

DO - 10.1016/j.neuroscience.2010.02.053

M3 - Article

C2 - 20219648

AN - SCOPUS:77951268235

SN - 0306-4522

VL - 167

SP - 946

EP - 953

JO - Neuroscience

JF - Neuroscience

IS - 3

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

Access to Document

Other files and links

Fingerprint

Cite this