Authors

Spence VA, Khan F, Kennedy G, Abbot NC, Belch JJF

Institution

Vascular Diseases Research Unit, The Institute of Cardiovascular Research, Ninewells Hospital and Medical School, Dundee, UK

Support

Studies reported here were funded by ME Research UK. Laser Doppler equipment was purchased by a grant from the Disability Aid Foundation. Further support was also received from the Sir John Fisher Foundation (Educational Grant).

Summary

The aetiology of chronic fatigue syndrome (CFS) remains controversial and a number of hypotheses have been put forward to explain it. Research into the condition is hindered by the considerable heterogeneity seen across patients but several reports have highlighted disturbances to cholinergic mechanisms in terms of central nervous system activity, neuromuscular function and autoantibodies to muscarinic cholinergic receptors. This paper examines an altogether separate function for acetylcholine and that is its role as an important and generalized vasodilator. Most diseases are accompanied by a blunted response to acetylcholine but the opposite is true for CFS. Such sensitivity is normally associated with physical training so the finding in CFS is anomalous and may well be relevant to vascular symptoms that characterise many patients. There are several mechanisms that might lead to ACh endothelial sensitivity in CFS patients and various experiments have been designed to unravel the enigma. These are reported here.

Publication

Prostaglandins, Leukotrienes and Essential Fatty Acids, 2004 Apr; 70(4): 403–7
Download full paper (pdf 259 KB)

© 2004, reproduced with permission from Elsevier. Access the journal from Science Direct

Comment by ME Research UK

CFS is currently defined exclusively by a number of non-specific symptoms that are common to many conditions, but there has been speculation that many of the neurological symptoms might be cholinergically mediated (1). This conjecture is supported by findings of increased levels of free choline in the central nervous system of CFS patients (2–4). As well as these neurological findings, however, there has been a recent report of autoantibodies specifically to muscarinic receptors in many CFS patients, suggesting that there might well be subgroups within the CFS construct that are associated with autoimmune abnormalities of cholinergic, muscarinic receptors (5). Apart from its neurotransmitter functions, acetylcholine is, of course, a well-established and prominent vasodilator whose action is dependent upon an intact layer of functioning endothelial cells that line the lumen of all blood vessels. This mini-review brings together a number of novel studies, examining blood vessel endothelial biology in CFS/ME patients, which have now been published by the research group at the University of Dundee, UK. This group has found clear abnormalities associated with a specific endothelium-dependent vasodilator — acetylcholine — and the review sets out to explain the biology and significance of the acetylcholine pathway as it affects endothelial cells, and what experiments are needed to unravel the mystery of the sensitivity seen in CFS/ME patients. The review is divided into 5 sections and a conclusion.

References

  1. Chaudhuri A, Majeed T, Dinan T, Behan PO. Chronic fatigue syndrome: a disorder of central cholinergic transmission. J Chronic Fatigue Syndrome 1997; 3: 3–16.
  2. Tomoda A, Miike T, Yamada E et al. Chronic fatigue syndrome in childhood. Brain Dev 2002; 22: 60–4.
  3. Puri BK, Counsell SJ, Zaman R et al. Relative increase in choline in the occipital cortex in chronic fatigue syndrome. Acta Psychiatr Scand 2002; 106: 224–6.
  4. Chaudhuri A, Cindon BR, Gow JW, Brennan D, Hadley DM. Proton magnetic resonance of basal ganglia in chronic fatigue syndrome. Neuroreport 2003; 14: 225–8.
  5. Tanaka S, Kuratsune H, Hidaka Y, Hakariya Y et al. Autoantibodies against muscarinic cholinergic receptor in chronic fatigue syndrome. Int J Mol Med 2003; 12: 225–30.

Read more (pdf 155 KB) in the Spring 2005 issue of Breakthrough.