Abstract
Among the neurotoxicants contained in tobacco smoke, if absorbed during pregnancy, nicotine significantly affects α7-nicotinic acetylcholine receptors, which play essential roles in the development of the brainstem regions receiving cholinergic projections in perinatal life. Immunohistochemical procedures for analysing formalin-fixed and paraffin-embedded brainstem samples from 68 fetuses and early newborns, with smoking and non-smoking mothers, who died of known and unknown causes, were carried out in order to determine if nicotine had activated the α7-nicotinic acetylcholine receptors. High α7-nicotinic acetylcholine receptor expression levels were only observed in the victims with smoking mothers. Frequently, these findings were associated with the hypoplasia of the brainstem structures controlling vital functions. The results of this study indicate that the exposition to nicotine in pregnancy exerts a strong direct effect on α7-nicotinic acetylcholine receptor activity especially in perinatal life and may be one of the primary risk factors leading to the sudden unexplained death of fetuses and newborns.
Highlights
To date, the “Lino Rossi” Research Center of Milan University, Italy, has examined over 200 cases of unexplained fetal and infant death, as it is the national reference center for the application and enforcement of the Italian Law 31/2006 “Regulations for diagnostic post mortem investigation in victims of sudden infant death syndrome (SIDS) and unexpected fetal death” [1]
The “Lino Rossi” Research Center of Milan University, Italy, has examined over 200 cases of unexplained fetal and infant death, as it is the national reference center for the application and enforcement of the Italian Law 31/2006 “Regulations for diagnostic post mortem investigation in victims of sudden infant death syndrome (SIDS) and unexpected fetal death” [1]. This law decrees that all infants suspected of SIDS who died suddenly in Italian regions within the first year of age as well as all fetuses who died after the 25th week of gestation without any apparent cause must undergo diagnostic post mortem investigations performed according to specific guidelines. The application of this protocol, which foresees an in-depth anatomo-pathological examination of the autonomic nervous system, including immunohistochemical techniques to highlight the expression of various functional markers, allowed for carrying out a wide range of research studies, many of which have highlighted the harmful effects of prenatal nicotine absorption on the autonomic nervous system in perinatal life
The aim of this study is to provide evidence of the primary mechanism underlying the perturbed development of brainstem substructures associated with nicotine absorption, especially focusing on neuronal nicotinic acetylcholine (Ach) receptors
Summary
The “Lino Rossi” Research Center of Milan University, Italy, has examined over 200 cases of unexplained fetal and infant death, as it is the national reference center for the application and enforcement of the Italian Law 31/2006 “Regulations for diagnostic post mortem investigation in victims of sudden infant death syndrome (SIDS) and unexpected fetal death” [1] This law decrees that all infants suspected of SIDS who died suddenly in Italian regions within the first year of age as well as all fetuses who died after the 25th week of gestation without any apparent cause must undergo diagnostic post mortem investigations performed according to specific guidelines. These receptors, widely expressed in the Toxics 2018, 6, 63; doi:10.3390/toxics6040063 www.mdpi.com/journal/toxics
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