Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats

We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testost...

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Main Authors: Pedro Espinosa, Roxana A. Silva, Nicole K. Sanguinetti, Francisca C. Venegas, Raul Riquelme, Luis F. González, Gonzalo Cruz, Georgina M. Renard, Pablo R. Moya, Ramón Sotomayor-Zárate
Format: Article
Language:English
Published: Wiley 2016-01-01
Series:Neural Plasticity
Online Access:http://dx.doi.org/10.1155/2016/4569785
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author Pedro Espinosa
Roxana A. Silva
Nicole K. Sanguinetti
Francisca C. Venegas
Raul Riquelme
Luis F. González
Gonzalo Cruz
Georgina M. Renard
Pablo R. Moya
Ramón Sotomayor-Zárate
author_facet Pedro Espinosa
Roxana A. Silva
Nicole K. Sanguinetti
Francisca C. Venegas
Raul Riquelme
Luis F. González
Gonzalo Cruz
Georgina M. Renard
Pablo R. Moya
Ramón Sotomayor-Zárate
author_sort Pedro Espinosa
collection DOAJ
description We sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.
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spelling doaj-art-8d87dbf4ab2e4e5ea50295f2e6b025482025-08-20T02:09:38ZengWileyNeural Plasticity2090-59041687-54432016-01-01201610.1155/2016/45697854569785Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male RatsPedro Espinosa0Roxana A. Silva1Nicole K. Sanguinetti2Francisca C. Venegas3Raul Riquelme4Luis F. González5Gonzalo Cruz6Georgina M. Renard7Pablo R. Moya8Ramón Sotomayor-Zárate9Laboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Alteraciones Reproductivas y Metabólicas, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Neurogenética, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileLaboratorio de Neuroquímica y Neurofarmacología, Centro de Neurobiología y Plasticidad Cerebral, Instituto de Fisiología, Facultad de Ciencias, Universidad de Valparaíso, 2360102 Valparaíso, ChileWe sought to determine the long-term changes produced by neonatal sex hormone administration on the functioning of midbrain dopaminergic neurons in adult male rats. Sprague-Dawley rats were injected subcutaneously at postnatal day 1 and were assigned to the following experimental groups: TP (testosterone propionate of 1.0 mg/50 μL); DHT (dihydrotestosterone of 1.0 mg/50 μL); EV (estradiol valerate of 0.1 mg/50 μL); and control (sesame oil of 50 μL). At postnatal day 60, neurochemical studies were performed to determine dopamine content in substantia nigra-ventral tegmental area and dopamine release in nucleus accumbens. Molecular (mRNA expression of tyrosine hydroxylase) and cellular (tyrosine hydroxylase immunoreactivity) studies were also performed. We found increased dopamine content in substantia nigra-ventral tegmental area of TP and EV rats, in addition to increased dopamine release in nucleus accumbens. However, neonatal exposure to DHT, a nonaromatizable androgen, did not affect midbrain dopaminergic neurons. Correspondingly, compared to control rats, levels of tyrosine hydroxylase mRNA and protein were significantly increased in TP and EV rats but not in DHT rats, as determined by qPCR and immunohistochemistry, respectively. Our results suggest an estrogenic mechanism involving increased tyrosine hydroxylase expression, either by direct estrogenic action or by aromatization of testosterone to estradiol in substantia nigra-ventral tegmental area.http://dx.doi.org/10.1155/2016/4569785
spellingShingle Pedro Espinosa
Roxana A. Silva
Nicole K. Sanguinetti
Francisca C. Venegas
Raul Riquelme
Luis F. González
Gonzalo Cruz
Georgina M. Renard
Pablo R. Moya
Ramón Sotomayor-Zárate
Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats
Neural Plasticity
title Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats
title_full Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats
title_fullStr Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats
title_full_unstemmed Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats
title_short Programming of Dopaminergic Neurons by Neonatal Sex Hormone Exposure: Effects on Dopamine Content and Tyrosine Hydroxylase Expression in Adult Male Rats
title_sort programming of dopaminergic neurons by neonatal sex hormone exposure effects on dopamine content and tyrosine hydroxylase expression in adult male rats
url http://dx.doi.org/10.1155/2016/4569785
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