Parkinson-like early autonomic dysfunction induced by vagal application of DOPAL in rats

CNS Neurosci Ther. 2021 May;27(5):540-551. doi: 10.1111/cns.13589. Epub 2021 Jan 21.

Abstract

Aim: To understand why autonomic failures, a common non-motor symptom of Parkinson's disease (PD), occur earlier than typical motor disorders.

Methods: Vagal application of DOPAL (3,4-dihydroxyphenylacetaldehyde) to simulate PD-like autonomic dysfunction and understand the connection between PD and cardiovascular dysfunction. Molecular and morphological approaches were employed to test the time-dependent alternation of α-synuclein aggregation and the ultrastructure changes in the heart and nodose (NG)/nucleus tractus solitarius (NTS).

Results: Blood pressure (BP) and baroreflex sensitivity of DOPAL-treated rats were significantly reduced accompanied with a time-dependent change in orthostatic BP, consistent with altered echocardiography and cardiomyocyte mitochondrial ultrastructure. Notably, time-dependent and collaborated changes in Mon-/Tri-α-synuclein were paralleled with morphological alternation in the NG and NTS.

Conclusion: These all demonstrate that early autonomic dysfunction mediated by vagal application of DOPAL highly suggests the plausible etiology of PD initiated from peripheral, rather than central site. It will provide a scientific basis for the prevention and early diagnosis of PD.

Keywords: DOPAL; Parkinson's disease; autonomic dysfunction; vagus; α-synuclein.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 3,4-Dihydroxyphenylacetic Acid / analogs & derivatives*
  • 3,4-Dihydroxyphenylacetic Acid / pharmacology
  • Animals
  • Autonomic Nervous System Diseases / etiology
  • Autonomic Nervous System Diseases / pathology*
  • Baroreflex / drug effects
  • Blood Pressure / drug effects
  • Electrocardiography
  • Hypotension, Orthostatic / physiopathology
  • Male
  • Mitochondria, Heart / pathology
  • Myocardium / pathology
  • Myocytes, Cardiac / pathology
  • Nodose Ganglion / pathology
  • Parkinson Disease, Secondary / complications
  • Parkinson Disease, Secondary / pathology*
  • Rats
  • Rats, Sprague-Dawley
  • Vagus Nerve*
  • alpha-Synuclein / biosynthesis
  • alpha-Synuclein / genetics

Substances

  • Snca protein, rat
  • alpha-Synuclein
  • 3,4-Dihydroxyphenylacetic Acid
  • 3,4-dihydroxyphenylacetaldehyde