Abnormalities in substance P neurokinin-1 receptor binding in key brainstem nuclei in sudden infant death syndrome related to prematurity and sex

Abstract

Sudden infant death syndrome (SIDS) involves failure of arousal to potentially life threatening events, including hypoxia, during sleep. While neuronal dysfunction and abnormalities in neurotransmitter systems within the medulla oblongata have been implicated, the specific pathways associated with autonomic and cardiorespiratory failure are unknown. The neuropeptide substance P (SP) and its tachykinin neurokinin-1 receptor (NK1R) have been shown to play an integral role in the modulation of homeostatic function in the medulla, including regulation of respiratory rhythm generation, integration of cardiovascular control, and modulation of the baroreceptor reflex and mediation of the chemoreceptor reflex in response to hypoxia. Abnormalities in SP neurotransmission may therefore result in autonomic dysfunction during sleep and contribute to SIDS deaths. [125I] Bolton Hunter SP autoradiography was used to map the distribution and density of the SP, NK1R to 13 specific nuclei intimately related to cardiorespiratory function and autonomic control in the human infant medulla of 55 SIDS and 21 control (non-SIDS) infants. Compared to controls, SIDS cases exhibited a differential, abnormal developmental profile of the SP/NK1R system in the medulla. Furthermore the study revealed significantly decreased NK1R binding within key medullary nuclei in SIDS cases, principally in the nucleus tractus solitarii (NTS) and all three subdivisions of the inferior portion of the olivo-cerebellar complex; the principal inferior olivary complex (PIO), medial accessory olive (MAO) and dorsal accessory olive (DAO). Altered NK1R binding was significantly influenced by prematurity and male sex, which may explain the increased risk of SIDS in premature and male infants. Abnormal NK1R binding in these medullary nuclei may contribute to the defective interaction of critical medullary mechanisms with cerebellar sites, resulting in an inability of a SIDS infant to illicit appropriate respiratory and motor responses to life threatening challenges during sleep. These observations support the concept that abnormalities in a multi-neurotransmitter network within key nuclei of the medullary homeostatic system may underlie the pathogenesis of a subset of SIDS cases.

Interaction of neurotransmitters and neurochemicals with lymphocytes

“…These G protein-coupled receptors include NK1, NK2 and NK3 (Hafidi et al, 2002;Harrison et al, 2004). Of these, NK1 has high affinity for substance P, and is the best characterised (Bright et al, 2017;Monastyrskaya et al, 2005). NK1 is expressed in neurons (Todd et al, 2000), endothelial cells (Greeno et al, 1993), smooth muscle cells (Maghni et al, 2003), fibroblasts (Liu et al, 2006) and epithelial cells (Bockmann, 2002).…”

<strong>SARS-Corona Virus-2 May Initially Infect Brainstem through Trigeminal Ganglion-Latency May Be Present-A New Perspective </strong>

“…SP and NK-1R regulates the breathing and cardiovascular control in medulla as a consequence of hypoxia.In a study conducted on SIDS victims, a significantly decreases in NK-1R binding within medullary nuclei in SIDS was observed as compared to control. Alteration in SP secretions and modulation may disturb the autonomic functionalities leading to lack of arousal and cause SIDS [41]. It explains a possible mechanism of causality in elderly patients due to Covid-19.…”

Neuropathological Developments in Sudden Infant Death Syndrome

“…Specifically, reduction of SP in SIDS infants in areas of the olivary nuclei that control head and neck movement may explain why SIDS infants fail to lift their heads away from challenging environments when prone. 69,70 These evaluations are not, however, part of the standard neuropathological evaluation of SIDS cases. It is also yet to be established how abnormalities in individual neurotransmitter systems may influence one another, or what the impact of a particular neurotransmitter dysfunction on other systems may be within the same or closely associated medullary nuclei.…”