Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains

This study investigated the effects of the pharmacological manipulation of noradrenergic activities on dopaminergic phenotypes in aged rats. Results showed that the administration of L-threo-3,4-dihydroxyphenylserine (L-DOPS) for 21 days significantly increased the expression of tyrosine hydroxylase...

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Autores principales:	Fei Zeng, Yan Fan, Russell W. Brown, Wesley Drew Gill, Jennifer B. Price, Thomas C. Jones, Meng-Yang Zhu
Formato:	article
Lenguaje:	EN
Publicado:	SAGE Publishing 2021
Materias:	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
Acceso en línea:	https://doaj.org/article/d978b88bdeb44b91a2c6dedadd05fb91
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spelling	oai:doaj.org-article:d978b88bdeb44b91a2c6dedadd05fb912021-11-23T23:03:33ZEffects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains1759-091410.1177/17590914211055064https://doaj.org/article/d978b88bdeb44b91a2c6dedadd05fb912021-11-01T00:00:00Zhttps://doi.org/10.1177/17590914211055064https://doaj.org/toc/1759-0914This study investigated the effects of the pharmacological manipulation of noradrenergic activities on dopaminergic phenotypes in aged rats. Results showed that the administration of L-threo-3,4-dihydroxyphenylserine (L-DOPS) for 21 days significantly increased the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum and substantia nigra (SN) of 23-month-old rats. Furthermore, this treatment significantly increased norepinephrine/DA concentrations in the striatum and caused a deficit of sensorimotor gating as measured by prepulse inhibition (PPI). Next, old rats were injected with the α2-adrenoceptor antagonist 2-methoxy idazoxan or β2-adrenoceptor agonist salmeterol for 21 days. Both drugs produced similar changes of TH and DAT in the striatum and SN. Moreover, treatments with L-DOPS, 2-methoxy idazoxan, or salmeterol significantly increased the protein levels of phosphorylated Akt in rat striatum and SN. However, although a combination of 2-methoxy idazoxan and salmeterol resulted in a deficit of PPI in these rats, the administration of 2-methoxy idazoxan alone showed an opposite behavioral change. The in vitro experiments revealed that treatments with norepinephrine markedly increased mRNAs and proteins of ATF2 and CBP/p300 and reduced mRNA and proteins of HDAC2 and HDAC5 in MN9D cells. A ChIP assay showed that norepinephrine significantly increased CBP/p300 binding or reduced HDAC2 and HDAC5 binding on the TH promoter. The present results indicate that facilitating noradrenergic activity in the brain can improve the functions of dopaminergic neurons in aged animals. While this improvement may have biochemically therapeutic indication for the status involving the degeneration of dopaminergic neurons, it may not definitely include behavioral improvements, as indicated by using 2-methoxy idazoxan only.Fei ZengYan FanRussell W. BrownWesley Drew Gill Jennifer B. PriceThomas C. JonesMeng-Yang ZhuSAGE PublishingarticleNeurosciences. Biological psychiatry. NeuropsychiatryRC321-571ENASN Neuro, Vol 13 (2021)
institution	DOAJ
collection	DOAJ
language	EN
topic	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571
spellingShingle	Neurosciences. Biological psychiatry. Neuropsychiatry RC321-571 Fei Zeng Yan Fan Russell W. Brown Wesley Drew Gill Jennifer B. Price Thomas C. Jones Meng-Yang Zhu Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains
description	This study investigated the effects of the pharmacological manipulation of noradrenergic activities on dopaminergic phenotypes in aged rats. Results showed that the administration of L-threo-3,4-dihydroxyphenylserine (L-DOPS) for 21 days significantly increased the expression of tyrosine hydroxylase (TH) and dopamine transporter (DAT) in the striatum and substantia nigra (SN) of 23-month-old rats. Furthermore, this treatment significantly increased norepinephrine/DA concentrations in the striatum and caused a deficit of sensorimotor gating as measured by prepulse inhibition (PPI). Next, old rats were injected with the α2-adrenoceptor antagonist 2-methoxy idazoxan or β2-adrenoceptor agonist salmeterol for 21 days. Both drugs produced similar changes of TH and DAT in the striatum and SN. Moreover, treatments with L-DOPS, 2-methoxy idazoxan, or salmeterol significantly increased the protein levels of phosphorylated Akt in rat striatum and SN. However, although a combination of 2-methoxy idazoxan and salmeterol resulted in a deficit of PPI in these rats, the administration of 2-methoxy idazoxan alone showed an opposite behavioral change. The in vitro experiments revealed that treatments with norepinephrine markedly increased mRNAs and proteins of ATF2 and CBP/p300 and reduced mRNA and proteins of HDAC2 and HDAC5 in MN9D cells. A ChIP assay showed that norepinephrine significantly increased CBP/p300 binding or reduced HDAC2 and HDAC5 binding on the TH promoter. The present results indicate that facilitating noradrenergic activity in the brain can improve the functions of dopaminergic neurons in aged animals. While this improvement may have biochemically therapeutic indication for the status involving the degeneration of dopaminergic neurons, it may not definitely include behavioral improvements, as indicated by using 2-methoxy idazoxan only.
format	article
author	Fei Zeng Yan Fan Russell W. Brown Wesley Drew Gill Jennifer B. Price Thomas C. Jones Meng-Yang Zhu
author_facet	Fei Zeng Yan Fan Russell W. Brown Wesley Drew Gill Jennifer B. Price Thomas C. Jones Meng-Yang Zhu
author_sort	Fei Zeng
title	Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains
title_short	Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains
title_full	Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains
title_fullStr	Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains
title_full_unstemmed	Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains
title_sort	effects of manipulation of noradrenergic activities on the expression of dopaminergic phenotypes in aged rat brains
publisher	SAGE Publishing
publishDate	2021
url	https://doaj.org/article/d978b88bdeb44b91a2c6dedadd05fb91
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Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains

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