The α3 and α4 nicotinic acetylcholine receptor (nAChR) subunits in the brainstem medulla of sudden infant death syndrome (SIDS)

Atqiya Aishah; Tina Hinton; Karen A Waters; Rita Machaalani

doi:10.1016/j.nbd.2019.01.010

The α3 and α4 nicotinic acetylcholine receptor (nAChR) subunits in the brainstem medulla of sudden infant death syndrome (SIDS)

Neurobiol Dis. 2019 May:125:23-30. doi: 10.1016/j.nbd.2019.01.010. Epub 2019 Jan 18.

Authors

Atqiya Aishah¹, Tina Hinton¹, Karen A Waters², Rita Machaalani³

Affiliations

¹ Discipline of Pharmacology, Faculty of Health and Medicine, The University of Sydney, NSW 2006, Australia; The Bosch Institute, Faculty of Health and Medicine, The University of Sydney, NSW 2006, Australia.
² Central Clinical School of Medicine, Faculty of Health and Medicine, The University of Sydney, NSW 2006, Australia.
³ The Bosch Institute, Faculty of Health and Medicine, The University of Sydney, NSW 2006, Australia; Central Clinical School of Medicine, Faculty of Health and Medicine, The University of Sydney, NSW 2006, Australia. Electronic address: rita.machaalani@sydney.edu.au.

PMID: 30665006
DOI: 10.1016/j.nbd.2019.01.010

Abstract

SIDS occurs in early infancy and predominantly during a sleep period. Abnormalities in nicotine receptor binding and in the expression of the nicotinic acetylcholine receptor (nAChR) subunits α7 and β2 have been reported in the brainstem of SIDS infants. This study focuses on the α3 and α4 nAChR subunits as α3 is important for early postnatal survival while α4 is crucial for nicotine-elicited antinociception and sleep-wake cycle regulation. Tissue from the rostral medulla of infants who died with a known cause of death (eSUDI, n = 7), and from SIDS classified as SIDS I (n = 8) and SIDS II (n = 27), was immunohistochemically stained for the α3 and α4 nAChR subunits and quantified in 9 nuclei comparing amongst these groups. The association with risk factors of sex, cigarette smoke exposure, upper respiratory tract infection (URTI), prone sleeping and bedsharing was also evaluated. Results showed that only α4 changes (increase) were evident in SIDS, occurring in the hypoglossal and cuneate nuclei of SIDS II infants and the nucleus of the spinal trigeminal tract of SIDS I infants. Amongst the SIDS infants, cigarette smoke exposure was only associated with decreased α4 in cribriform fibre tracts, while sex and bedsharing were associated with increases in α3 in the dorsal motor nucleus of the vagus and solitary nucleus, respectively. Combined, these findings suggest that abnormalities in endogenous acetylcholine synthesis and regulation may underlie the altered α3 and α4 nAChR subunit expressions in the SIDS brainstem medulla since the changes were not related to cigarette smoke exposure.

Keywords: Brain; CHRNA; Immunohistochemistry; Nicotine; Smoking; nACh.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Female
Humans
Infant
Infant, Newborn
Male
Medulla Oblongata / metabolism*
Nicotiana / adverse effects
Receptors, Nicotinic / analysis
Receptors, Nicotinic / biosynthesis*
Smoke / adverse effects
Sudden Infant Death / etiology*

Substances

Receptors, Nicotinic
Smoke
nicotinic acetylcholine receptor alpha4 subunit