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Effects of Manipulation of Noradrenergic Activities on the Expression of Dopaminergic Phenotypes in Aged Rat Brains.
Zeng, Fei; Fan, Yan; Brown, Russell W; Drew Gill, Wesley; Price, Jennifer B; Jones, Thomas C; Zhu, Meng-Yang.
Afiliación
  • Zeng F; Department of Neurology, Renmin Hospital of the Wuhan University, China.
  • Fan Y; Departments of Biomedical Sciences, Quillen College of Medicine, 4154East Tennessee State University, USA.
  • Brown RW; Departments of Biomedical Sciences, Quillen College of Medicine, 4154East Tennessee State University, USA.
  • Drew Gill W; Department of Biochemistry, Nantong University College of Medicine, China.
  • Price JB; Departments of Biomedical Sciences, Quillen College of Medicine, 4154East Tennessee State University, USA.
  • Jones TC; Departments of Biomedical Sciences, Quillen College of Medicine, 4154East Tennessee State University, USA.
  • Zhu MY; Department of Biological Sciences, College of Arts and Sciences, 4154East Tennessee State University, USA.
ASN Neuro ; 13: 17590914211055064, 2021.
Article en En | MEDLINE | ID: mdl-34812056
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 ß2-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.
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dopamina / Norepinefrina Límite: Animals Idioma: En Revista: ASN Neuro Asunto de la revista: NEUROLOGIA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos
Texto completo
Añadir a Mi BVS
Imprimir
XML
PubMed Links
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Texto completo: 1 Colección: 01-internacional Base de datos: MEDLINE Asunto principal: Dopamina / Norepinefrina Límite: Animals Idioma: En Revista: ASN Neuro Asunto de la revista: NEUROLOGIA / QUIMICA Año: 2021 Tipo del documento: Article País de afiliación: China Pais de publicación: Estados Unidos