Central and peripheral chemoreceptors in sudden infant death syndrome

Abstract

The pathogenesis of sudden infant death syndrome (SIDS) has been ascribed to an underlying biological vulnerability to stressors during a critical period of development. This paper reviews the main data in the literature supporting the role of central (e.g. retrotrapezoid nucleus, serotoninergic raphe nuclei, locus coeruleus, orexinergic neurons, ventral medullary surface, solitary tract nucleus) and peripheral (e.g. carotid body) chemoreceptors in the pathogenesis of SIDS. Clinical and experimental studies indicate that central and peripheral chemoreceptors undergo critical development during the initial postnatal period, consistent with the age range of SIDS (<1 year). Most of the risk factors for SIDS (gender, genetic factors, prematurity, hypoxic/hyperoxic stimuli, inflammation, perinatal exposure to cigarette smoke and/or substance abuse) may structurally and functionally affect the developmental plasticity of central and peripheral chemoreceptors, strongly suggesting the involvement of these structures in the pathogenesis of SIDS. Morphometric and neurochemical changes have been found in the carotid body and brainstem respiratory chemoreceptors of SIDS victims, together with functional signs of chemoreception impairment in some clinical studies. However, the methodological problems of SIDS research will have to be addressed in the future, requiring large and highly standardized case series. Up-to-date autopsy protocols should be produced, involving substantial, and exhaustive sampling of all potentially involved structures (including peripheral arterial chemoreceptors). Morphometric approaches should include unbiased stereological methods with three-dimensional probes. Prospective clinical studies addressing functional tests and risk factors (including genetic traits) would probably be the gold standard, allowing markers of intrinsic or acquired vulnerability to be properly identified.

The Role of Maternal Smoking in Sudden Fetal and Infant Death Pathogenesis

“…The carotid bodies can also be adversely affected by tobacco exposure. Smoke exposure can lead to abnormal maturation and neurotransmitter levels such as dopamine, leaving infants more vulnerable to hypoxic states (58,(79)(80)(81). These findings may further explain the impaired arousal observed in smoke-exposed infants in response to hypoxia (24,25).…”

“…Brainstem Neuropathological studies of both SIUDS and SIDS cases have highlighted both hypoplasia, increased apoptotic figures and abnormal functioning in a number of brainstem nuclei (52,56,58). All these abnormalities have been found to be greater following smoking in pregnancy.…”

Genetic variants in eleven central and peripheral chemoreceptor genes in sudden infant death syndrome

“… 16 In addition, the vulnerable phase of carotid body development takes place during the same period where the risk for SIDS is at its’ highest. 17 In chemoreceptive cells, membrane proteins, such as ion channels and receptor proteins, are indispensable for the measurement of changes to the partial pressure of oxygen (pO 2 ), carbon dioxide (pCO 2 ) or hydrogen ions (pH) in the arterial blood or brain tissue to either activate or inhibit the central pattern generator (CPG). 18 The chemo-sensitive cells in the carotid body are the so-called type 1 cells (glomus cells), which are mitochondria-rich cells expressing numerous different ion channels, including TASK (Twik-associated acid-sensitive K + channel) channels (TASK-1/TASK-3), calcium- and voltage-activated K + channels (Maxi-K + ), voltage-gated Na + channels (Na v ), and L- and N-type Ca 2+ channels.…”

Ablation of Zfhx4 results in early postnatal lethality by disrupting the respiratory center in mice

“…Some human disorders involve defects in the central control of breathing, such as central hypoventilation syndrome (CCHS) ( Ramanantsoa and Gallego, 2013 ), central sleep apnea syndrome ( Wuyam et al, 2000 ; Yap and Fleetham, 2001 ), and some cases of sudden infant death syndrome ( Calton et al, 2016 ; Porzionato et al, 2018 ). CCHS, which is often present at birth, is a genetic disease in which the brain fails to properly control breathing to maintain healthy levels of oxygen and carbon dioxide, especially during sleep, and a mutation in PHOX2B is the only confirmed heterozygous mutation causing CCHS ( Amiel et al, 2003 ; Trochet et al, 2005 ; Weese-Mayer et al, 2017 ).…”