EXPRESSION OF SUBSTANCE P IN BRAINSTEMS OF VICTIMS OF SUDDEN UNEXPLAINED PERINATAL DEATH

Sudden perinatal death including SIDS is a rare but lethal syndrome and there is no symptom of this disorder until the fatal outcome has occurred. Epidemiological, genetic, molecular and pathological studies conducted so far give us some possible explanations about it but are inadequate to explain it completely. Brainstem etiology is a mostly accepted hypothesis to induce sudden perinatal death. We investigated the immunohistochemical expression of substance P (SP) in the brainstems of 56 subjects aged from 17 gestational weeks to 10 postnatal months, died of unknown (sudden unexplained perinatal deaths and SIDS) and known causes (controls). The goals of this study were to obtain basic information about the expression of the SP during the first phases of human nervous system development; to evaluate whether there are altered manifestations of this neuromodulator in victims of sudden death; to verify the correlation with maternal cigarette smoking and to see the evolutionary aspects of SP gene (TAC1) through computational analysis. Immunohistochemistry demonstrated SP-immunoreactivity in correspondence of the caudal trigeminal nucleus area, with progressive increase in density of positive fibers of the corresponding tract from fetal life to first postnatal months. So, we first delineated the structure of the human trigeminal nucleus, so far little investigated, and provided essential data on its morphologic and functional development. Nevertheless, a negativity or low SP-positivity of the tract fibres was detectable in a wide subset of SIDS and, conversely, high SP-expression in a wide subset of sudden fetal deaths. Therefore we postulate, on the basis of these results, the functional importance of the SP in the early phases of central nervous system development and in the regulation of autonomic functions. Besides, the observation of a significant correlation between sudden unexplained death, altered SP staining and maternal smoking, prompted us to suppose a close relation between smoking absorption in utero and decrease of the functional activity of the trigeminal nucleus, leading to sudden death during pregnancy and in the first months of life. Computational analysis suggests that SP encoding gene (TAC1) is a singleton, appeared in vertebrates and is more prone to induce neuropathologies along with its interactors, if mutated or functionally altered, as it is located mostly in brain.