Cholinesterases as Biomarkers for Parasympathetic Dysfunction and Inflammation-Related Disease

Abstract

Accumulating evidence suggests parasympathetic dysfunction and elevated inflammation as underlying processes in multiple peripheral and neurological diseases. Acetylcholine, the main parasympathetic neurotransmitter and inflammation regulator, is hydrolyzed by the two closely homologous enzymes, acetylcholinesterase and butyrylcholinesterase (AChE and BChE, respectively), which are also expressed in the serum. Here, we consider the potential value of both enzymes as possible biomarkers in diseases associated with parasympathetic malfunctioning. We cover the modulations of cholinesterase activities in inflammation-related events as well as by cholinesterase-targeted microRNAs. We further discuss epigenetic control over cholinesterase gene expression and the impact of single-nucleotide polymorphisms on the corresponding physiological and pathological processes. In particular, we focus on measurements of circulation cholinesterases as a readily quantifiable readout for changes in the sympathetic/parasympathetic balance and the implications of changes in this readout in health and disease. Taken together, this cumulative know-how calls for expanding the use of cholinesterase activity measurements for both basic research and as a clinical assessment tool.

Decline in Serum Cholinesterase Activities Predicts 2-Year Major Adverse Cardiac Events

“…In past studies, we demonstrated the close correlation between our biomarkers and parallel physiological variables such as resting and recovery heart rate after stress testing (21,22,36).…”

“…Activation of this "cholinergic reflex" has been shown to alleviate inflammatory disease, including endotoxemia and septic peritonitis (34). However, hyperactivation of this suppressive effect may also increase the susceptibility to subsequent infection (35,36).…”

Self-forgiveness and forgiveness-seeking in response to rumination: Cardiac and emotional responses of transgressors

“…However, vagal deregulation has been associated with disruption in several measures of biopsychosocial well-being, such as positive emotions, social connectedness (Kok et al, 2013), satisfaction with life, depression, and global functioning (Kogan, Gruber, Shallcross, Jord, & Mauss, 2013). Some studies also suggest that parasympathetic deregulation may contribute to physical disorders such as hypertension due to an increase in cardiac output (Brindle et al, 2014), and a number of disorders associated with inflammatory processes (Shenhar-Tsarfaty et al, 2014). These observations suggest that ruminating about one's wrongdoing may also negatively impact emotional and physical well-being.…”

“…was less relevant. Therefore, seeking forgiveness as a humbly repentant process -independent from receiving forgiveness or not -could improve well-being and physical health by promoting vagal upregulation (Kogan et al, 2013;Kok et al, 2013;Shenhar-Tsarfaty et al, 2014). emotionally, valence during rumination was negative, and it became even more negative during the begrudged condition.…”

N-palmitoyl serotonin alleviates scopolamine-induced memory impairment via regulation of cholinergic and antioxidant systems, and expression of BDNF and p-CREB in mice

“…Separately, recent studies suggested the implication of cholinergic signaling in anti-inflammatory action by showing that AChE mRNA-targeting miRNA-132, which would reduce AChE mRNA expression, could attenuate the inflammation [50][51][52].…”