Nicotinic Receptor Abnormalities in the Cerebellar Cortex of Sudden Unexplained Fetal and Infant Death Victims—Possible Correlation With Maternal Smoking

Abstract

Nicotinic acetylcholine receptors (nAChRs) are cationic channels of the neuronal cell membrane, differentially expressed in the central nervous system which, when activated by endogenous acetylcholine or exogenous nicotine, are able to enhance cholinergic transmission. The aim of this study was to investigate in human perinatal age the immunohistochemical expression of the α7-nAChR subtype, given its involvement in neuronal differentiation and its significant vulnerability to the toxic effects of nicotine. Thirty fetuses (with a gestational age between 25 and 40 weeks) and 35 infants (1–6 months old), suddenly died of known (controls) and unknown causes (unexplained deaths), with smoking and nonsmoking mothers, were included in this study. A negative or low immunoexpression of α7-nAChRs, indicative of their inactivation, was observed in the granular layers of the cerebellar cortex in 66% of the sudden unexplained perinatal deaths and 11% of the controls. A high correlation was also observed between these findings and maternal smoking. Apart from the well-known adverse effects of nicotine exposure during pregnancy, it may also cause significant alterations in cerebellar cholinergic transmission in areas of the brain involved in vital functions. These events may give us insights into the pathogenetic mechanisms leading to sudden unexplained fetal and infant death.

Neurobiological Alterations Of The Substantia Nigra In Sudden Infant Death Syndrome

“…This study highlights for the first time the important involvement of the SNpc in SIDS pathogenesis and, as already reported in our previous studies (43)(44)(45)(46)(47)(48)(49), confirms that cigarette smoke absorption may have strongly influenced the results here presented. In fact, all the SIDS cases with decreased neuronal density, negative TH and NM expression and with mitotic neurons in the SNpc were born to smoking mothers.…”

“…In fact, in our SIDS cohort, a very low expression of the TH enzyme, indicative of DA deficit, was detected in 80% of cases with proven nicotine absorption. Our previous SIDS studies revealed a close correlation between maternal smoking, especially during pregnancy, and defects in the morphological/functional development of various nervous system structures (43)(44)(45)(46)(47)(48)(49). This study enhances our knowledge on the devastating effect of cigarette smoking and reinforces our awareness that once nicotine crosses the blood-brain barrier, it can harm and disactivate important brain centers which are crucial to perform the vital activities.…”

Neuropathology of Early Sudden Infant Death Syndrome—Hypoplasia of the Pontine Kolliker-Fuse Nucleus: A Possible Marker of Unexpected Collapse during Skin-to-Skin Care

“…Other sections were saved and stained as deemed necessary for the morphometric evaluations, as indicated later, and also for further investigations, such as the immunohistochemical characterization of specific receptors that are differently expressed in sudden perinatal death victims and controls. [20][21][22]…”

Substantia Nigra Abnormalities Provide New Insight on the Neural Mechanisms Underlying the Sleep-Arousal Phase Dysfunctions in Sudden Infant Death Syndrome

“…Accordingly, experimental studies have shown that in utero exposure to maternal smoking is associated with neuronal mitotic abnormalities and increased programmed cell death with consequent reduction of the neuronal content (Roy et al, 1998;Chatterton et al, 2017). Moreover, our previous SIDS studies revealed a close correlation between maternal smoking during pregnancy and defects in the morphological/functional development of various nervous system structures (Lavezzi et al, 2010(Lavezzi et al, , 2012(Lavezzi et al, , 2013b(Lavezzi et al, , 2013c(Lavezzi et al, , 2017Lavezzi, 2018). This study enhances our knowledge on the devastating effect of cigarette smoking and reinforces our awareness that once nicotine crosses the blood-brain barrier, it can harm and deactivate important brain centers which are crucial to perform the vital activities.…”