Serotonergic brainstem abnormalities in Northern Plains Indians with the sudden infant death syndrome.

The rate of the sudden infant death syndrome (SIDS) among American Indian infants in the Northern Plains is almost 6 times higher than in U.S. white infants. In a study of infant mortality among Northern Plains Indians, we tested the hypothesis that receptor binding abnormalities to the neurotransmitter serotonin (5-HT) in SIDS cases, compared with autopsied controls, occur in regions of the medulla oblongata that contain 5-HT neurons and that are critical for the regulation of cardiorespiration and central chemosensitivity during sleep, i.e. the medullary 5-HT system. Tritiated-lysergic acid diethylamide binding to 5-HT(1A-D) and 5-HT2 receptors was measured in 19 brainstem nuclei in 23 SIDS and 6 control infants using tissue receptor autoradiography. Binding in the arcuate nucleus, a part of the medullary 5-HT system along the ventral surface, in the SIDS infants (mean age-adjusted binding 7.1 +/- 0.8 fmol/mg tissue, n = 23) was significantly lower than in controls (mean age-adjusted binding 13.1 +/- 1.6 fmol/mg tissue, n = 5) (p = 0.003). Binding also demonstrated significant diagnosis x age interactions (p < 0.04) in 4 other nuclei that are components of the 5-HT system. These data suggest that medullary 5-HT dysfunction can lead to sleep-related, sudden death in affected SIDS infants, and confirm the same binding abnormalities reported by us in a larger dataset of non-American Indian SIDS and control infants. This study also links 5-HT abnormalities in the arcuate nucleus with exposure to adverse prenatal exposures, i.e. cigarette smoking (p = 0.011) and alcohol (p = 0.075), during the periconceptional period or throughout pregnancy. Prenatal exposure to cigarette smoke and/or alcohol may contribute to abnormal fetal medullary 5-HT development in SIDS infants.

Anatomic relationships of the human nucleus of the solitary tract in the medulla oblongata: a DiI labeling study.

The nucleus of the solitary tract (nTS) is a major site of brainstem control of vital functions (e.g., cardiovascular reflexes and respiration). We examined anatomic relationships of the human nucleus of the solitary tract, using a bidirectional lipophilic fluorescent tracer 1-1'-dioctadecyl-3,3,3',3'-tetramethylindocarbocyanine perchlorate (DiI) in 10 postmortem human fetal midgestational medullae oblongatae. Labeling by diffusion of DiI from the nucleus of the solitary tract included: (1) neuropil of all future subdivisions of the nucleus of the solitary tract ipsilateral to the DiI crystal; (2) stellate cells in the caudal raphe at the junction of the nucleus raphe pallidus and the arcuate nucleus at the ventral medullary surface, as well as single fibers along the caudal raphe and the arcuate nucleus; (3) cells and fibers in other medullary areas related to autonomic and respiratory control, including the dorsal motor nucleus of the vagus, nucleus ambiguus complex/ventral respiratory group, rostral ventrolateral medulla (RVLM) and caudal ventrolateral medulla (CVLM), and medullary reticular formation. The pattern of connections of the nucleus of the solitary tract already established by midgestation in the human fetus is consistent with the pattern previously demonstrated in adult experimental animals. A major finding of the study is that of the stellate cells at the junction of nucleus raphe pallidus and the arcuate nucleus at the ventral medullary surface, which project to the nucleus of the solitary tract, and could be homologous to chemosensitive serotonergic neurons at the midline ventral medullary surface of experimental animals. This connection between the ventral caudal raphe and the nucleus of the solitary tract may participate in chemoreception and central regulation of cardiorespiratory reflexes during human perinatal development; it is, therefore, relevant to the study of sudden infant death syndrome (SIDS).