Cardiac Muscarinic Receptor Overexpression in Sudden Infant Death Syndrome

Abstract

BackgroundSudden infant death syndrome (SIDS) remains the leading cause of death among infants less than 1 year of age. Disturbed expression of some neurotransmitters and their receptors has been shown in the central nervous system of SIDS victims but no biological abnormality of the peripheral vago-cardiac system has been demonstrated to date. The present study aimed to seek vago-cardiac abnormalities in SIDS victims. The cardiac level of expression of muscarinic receptors, as well as acetylcholinesterase enzyme activity were investigated.Methodology/Principal FindingsLeft ventricular samples and blood samples were obtained from autopsies of SIDS and children deceased from non cardiac causes. Binding experiments performed with [3H]NMS, a selective muscarinic ligand, in cardiac membrane preparations showed that the density of cardiac muscarinic receptors was increased as shown by a more than doubled Bmax value in SIDS (n = 9 SIDS versus 8 controls). On average, the erythrocyte acetylcholinesterase enzyme activity was also significantly increased (n = 9 SIDS versus 11 controls).ConclusionsIn the present study, it has been shown for the first time that cardiac muscarinic receptor overexpression is associated with SIDS. The increase of acetylcholinesterase enzyme activity appears as a possible regulatory mechanism.

Exome-Wide Rare Variant Analyses in Sudden Infant Death Syndrome

“…[24] In 2010, cardiac muscarinic receptor over-expression in left ventricular heart samples was shown to be associated with SIDS. [45] In 1995, Kinney et al provided evidence that deficiency of muscarinic receptor binding in the arcuate nucleus of the medulla may be associated with an increase in the probability of death from SIDS. [46]…”

Autonomic maturation from birth to 2 years: normative values

“…The links with molecular research analyzes contributions of inhibitors neurotransmitters of cardiorespiratory control, in the genesis of both apnea and bradycardia as GABA γ aminobutyric acid, adenosine, serotonin, endorphins and prostaglandins [16, 17] with the identification of an abnormal serotonergic response in the bulbar and arcuate nucleus of the hypothalamus in as much as 50% of the cases, presumably linked to genetic polymorphisms [18, 19, 20, 21]. In that view, overexpression of cardiac muscarinic receptors as well as an increased enzymatic acetylcholinesterase activity have been reported [22]. Regardless of the fetal risk associated with autonomic dysfunction, the study of the child autonomic status is also of great interest in many clinical situations as frequent as infections, sepsis [23, 24], chronic inflammatory [25] diseases or type 1 diabetes [26] in which impaired autonomic control and increased risk for cardiovascular disease are reported.…”

Animal Models for Assessment of Infection and Inflammation: Contributions to Elucidating the Pathophysiology of Sudden Infant Death Syndrome

“…A strain of rabbits was developed to examine the effect of cardiac muscarinic receptors on autonomic tone. Similar to infants dying from SIDS, these rabbits had over-expression of muscarinic receptors that was most pronounced between the fifth and the seventh week of life, a time of increased mortality in the rabbits ( 99 ). Abnormal autonomic development from maternal smoking during pregnancy might result in infants being unable to arouse and respond to a physiologic insult such as a drop in blood pressure, hypoxia, infection, or overheating.…”