Pure autonomic failure (PAF) is a rare sporadic disorder characterized by autonomic failure in the absence of a movement disorder or dementia and is associated with very low plasma norepinephrine (NE) levels—suggesting widespread sympathetic denervation, however due to its rarity the pathology remains poorly elucidated. We sought to correlate clinical and neurochemical findings with sympathetic nerve protein abundances, accessed by way of a forearm vein biopsy, in patients with PAF and in healthy controls and patients with multiple systems atrophy (MSA) in whom sympathetic nerves are considered intact. The abundance of sympathetic nerve proteins, extracted from forearm vein biopsy specimens, in 11 patients with PAF, 8 patients with MSA and 9 age-matched healthy control participants was performed following a clinical evaluation and detailed evaluation of sympathetic nervous system function, which included head-up tilt (HUT) testing with measurement of plasma catecholamines and muscle sympathetic nerve activity (MSNA) in addition to haemodynamic assessment to confirm the clinical phenotype. PAF participants were found to have normal abundance of the NE transporter (NET) protein, together with very low levels of tyrosine hydroxylase (TH) (P<0.0001) and reduced vesicular monoamine transporter 2 (VMAT2) (P<0.05) protein expression compared with control and MSA participants. These findings were associated with a significantly higher ratio of plasma 3,4-dihydroxyphenylglycol (DHPG):NE in PAF participants when compared with controls (P<0.05). The finding of normal NET abundance in PAF suggests intact sympathetic nerves but with reduced NE synthesis. The finding of elevated plasma ratio of DHPG:NE and reduced VMAT2 in PAF indicates a shift towards intraneuronal NE metabolism over sequestration in sympathetic nerves and suggests that sympathetic dysfunction may occur ahead of denervation.
Skip Nav Destination
Article navigation
January 2018
-
Cover Image
Cover Image
Oleic-acid-treated HepG2 cells immunostained for PGC-1α (PPARγ co-activator-1 α). In Clinical Science volume 132, issue 1, the results of work by Bernardi et al. include reporting that the protein TRAIL (TNF-related apoptosis inducing ligand) increases the expression of PGC-1α in HepG2 cells cultured with oleic acid. Overall, the article points to a potential therapeutic role for TRAIL against impaired glucose tolerance and non-alcoholic fatty liver disease; for details see pages 69–83.
Research Article|
January 02 2018
Does sympathetic dysfunction occur before denervation in pure autonomic failure?
Ling Guo;
Ling Guo
1Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
Search for other works by this author on:
Murray D. Esler;
Murray D. Esler
1Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
Search for other works by this author on:
Carolina Sari;
Carolina Sari
1Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
Search for other works by this author on:
Sarah Phillips;
Sarah Phillips
1Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
2Iverson Health Innovation Research Institute, Faculty of Health, Arts and Design, Swinburne University of Technology, P.O. Box 218, Hawthorn, Victoria, 3122, Australia
Search for other works by this author on:
Elisabeth A. Lambert;
Elisabeth A. Lambert
1Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
2Iverson Health Innovation Research Institute, Faculty of Health, Arts and Design, Swinburne University of Technology, P.O. Box 218, Hawthorn, Victoria, 3122, Australia
Search for other works by this author on:
Nora E. Straznicky;
Nora E. Straznicky
1Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
Search for other works by this author on:
Gavin W. Lambert;
Gavin W. Lambert
1Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
2Iverson Health Innovation Research Institute, Faculty of Health, Arts and Design, Swinburne University of Technology, P.O. Box 218, Hawthorn, Victoria, 3122, Australia
Search for other works by this author on:
Susan J. Corcoran
1Human Neurotransmitters Laboratory, Baker Heart and Diabetes Institute, P.O. Box 6492, St Kilda Rd Central, Melbourne, Victoria 8008, Australia
Correspondence: Susan J. Corcoran ([email protected])
Search for other works by this author on:
Publisher: Portland Press Ltd
Received:
March 21 2017
Revision Received:
November 03 2017
Accepted:
November 17 2017
Accepted Manuscript online:
November 21 2017
Online ISSN: 1470-8736
Print ISSN: 0143-5221
© 2018 The Author(s). Published by Portland Press Limited on behalf of the Biochemical Society
2018
Clin Sci (Lond) (2018) 132 (1): 1–16.
Article history
Received:
March 21 2017
Revision Received:
November 03 2017
Accepted:
November 17 2017
Accepted Manuscript online:
November 21 2017
Citation
Ling Guo, Murray D. Esler, Carolina Sari, Sarah Phillips, Elisabeth A. Lambert, Nora E. Straznicky, Gavin W. Lambert, Susan J. Corcoran; Does sympathetic dysfunction occur before denervation in pure autonomic failure?. Clin Sci (Lond) 16 January 2018; 132 (1): 1–16. doi: https://doi.org/10.1042/CS20170240
Download citation file:
Sign in
Don't already have an account? Register
Sign in to your personal account
You could not be signed in. Please check your email address / username and password and try again.
Could not validate captcha. Please try again.
Biochemical Society Member Sign in
Sign InSign in via your Institution
Sign in via your InstitutionGet Access To This Article
Cited By
Open Access for all
We offer compliant routes for all authors from 2025. With library support, there will be no author nor reader charges in 5 journals. Check here |
![]() |