Altered Development of Mesencephalic Dopaminergic Neurons in SIDS: New Insights into Understanding Sudden Infant Death Pathogenesis.

Anna Maria Lavezzi

doi:10.3390/biomedicines9111534

Abstract

Sudden infant death syndrome (SIDS) is defined as the unexpected sudden death of an infant under 1 year of age that remains unexplained after a thorough case investigation. The SIDS pathogenesis is still unknown; however, abnormalities in brain centers that control breathing and arousal from sleep, including dramatic changes in neurotransmitter levels, have been supposed in these deaths. This is the first study focusing on mesencephalic dopaminergic neurons, so far extensively studied only in animals and human neurological diseases, in SIDS. Dopaminergic structures in midbrain sections of a large series of sudden infant deaths (36 SIDS and 26 controls) were identified using polyclonal rabbit antibodies against tyrosine hydroxylase, the rate-limiting enzyme in catecholamine biosynthesis, and the dopamine transporter, a membrane protein specifically expressed in dopaminergic cells. Dopamine-immunolabeled neurons were observed concentrated in two specific structures: the pars compacta of the substantia nigra and in the subnucleus medialis of the periaqueductal gray matter. Anatomical and functional degenerations of dopaminergic neurons in these regions were observed in most SIDS cases but never in controls. These results indicate that dopamine depletion, which is already known to be linked especially to Parkinson’s disease, is strongly involved even in SIDS pathogenesis.

Highlights

It is important to note that tyrosine hydroxylase (TH) expression in both Sudden infant death syndrome (SIDS) and controls was almost always in agreement with dopamine transporter (DAT) expression, indicating that the catecholaminergic neurons identified by TH-immunohistochemistry were dopaminergic
Notable levels of both TH and DAT markers were found in controls concentrated in perikarya and processes of neurons located in two specific mesencephalic regions: (1) the pars compacta of the substantia nigra (SNpc), a structure located adjacent to the superior peduncles, and (2) a subpopulation of neurons in the anterolateral part of the periaqueductal gray (PAG), which is an area of the gray matter surrounding the cerebral aqueduct of Sylvius, namely the subnucleus medialis (PAGsm)
The identification of the Mesencephalic Dopaminergic (mDA) neurons in newborns was achieved by applying the immunohistochemistry for tyrosine hydroxylase (TH) and, since this enzyme is expressed in other catecholaminergic neurons, for the dopamine transporter (DAT), a plasma membrane protein selectively expressed in DA neurons [21,22,23]

Summary

Introduction

Sudden infant death syndrome (SIDS) is defined as the death of an apparently healthy infant under 1 year of age, usually occurring during sleep, that remains unexplained after a thorough case investigation that includes a death scene assessment, an autopsy, and a clinical history review [1,2]. Little is known about SIDS pathogenesis except that it is probably caused by a combination of many circumstances and in particular, it affects babies who are vulnerable to various environmental stresses during a critical developmental period [3]. The way that parents can reduce the risk of SIDS is by not smoking while pregnant and, after birth, by placing the baby on the back when asleep [4,5]

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