Cardiac Noradrenaline Turnover and Heat Shock Protein 27 Phosphorylation in Dyskinetic Monkeys

Mov Disord. 2020 Apr;35(4):698-703. doi: 10.1002/mds.27958. Epub 2019 Dec 24.

Abstract

Background: Autonomic dysfunction is a well-known dominant symptom in the advanced stages of Parkinson's disease. However, the role of cardiac sympathetic nerves still needs to be elucidated.

Objectives: To evaluate cardiac sympathetic response in Parkinsonian and dyskinetic monkeys.

Methods: Adult male monkeys were divided into 1 of the following 3 groups: controls, 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine-treated monkeys, and 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine+levodopa-treated animals. Noradrenaline, its metabolite normetanephrine, and phospho-Heat shock proten 27 (p-Hsp27) at serine 82 levels were analyzed in the left and right ventricles of the heart. Tyrosine hydroxylase immunohistochemistry was performed in the ventral mesencephalon.

Results: The results were the following: (1) 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine intoxication significantly increased normetanephrine levels and decreased noradrenaline turnover in the right ventricle without changes in the left ventricle; however, (2) levodopa treatment decreased noradrenaline levels and enhanced the normetanephrine/noradrenaline ratio in parallel with a very significant increase of Hsp27 activity in both ventricles.

Conclusions: Levodopa treatment could induce protective cardiac effects through the increased Hsp27 activity. © 2019 International Parkinson and Movement Disorder Society.

Keywords: l-dopa; Hsp27; NA turnover; Parkinson's disease; TH.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Animals
  • Dyskinesias / metabolism*
  • HSP27 Heat-Shock Proteins*
  • Levodopa
  • Macaca fascicularis
  • Male
  • Norepinephrine*
  • Phosphorylation
  • Tyrosine 3-Monooxygenase / metabolism

Substances

  • HSP27 Heat-Shock Proteins
  • Levodopa
  • 1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine
  • Tyrosine 3-Monooxygenase
  • Norepinephrine