Decreased serotonergic receptor binding in rhombic lip-derived regions of the medulla oblongata in the sudden infant death syndrome

The sudden infant death syndrome (SIDS) is postulated to result from a fail ure of homeostatic responses to life-threatening challenges (e.g. asphyxia, hypercapnia) during sleep. The ventral medulla participates in sleep-relat ed homeostatic responses, including chemoreception, arousal, airway reflex control, thermoregulation, respiratory drive, and blood pressure regulation , in part via serotonin and its receptors. The ventral medulla in humans co ntains the arcuate nucleus, in which we have shown isolated defects in musc arinic and kainate receptor binding in SIDS victims. We also have demonstra ted that the arcuate nucleus is anatomically linked to the nucleus raphe ob scurus, a medullary region with serotonergic neurons. We tested the hypothe sis that serotonergic receptor binding is decreased in both the arcuate nuc leus and nucleus raphe obscurus in SIDS victims. Using quantitative autorad iography, H-3-lysergic acid diethylamide (H-3-LSD binding) to serotonergic receptors (5-HT1A-D and 5-HT2 subtypes) was measured blinded in 19 brainste m nuclei. Cases were classified as SIDS (n = 52), acute controls (infants w ho died suddenly and in whom a complete autopsy established a cause of deat h) (n = 15), or chronic cases with oxygenation disorders (n = 17). Serotone rgic binding was significantly lowered in the SIDS victims compared with co ntrols in the arcuate nucleus (SIDS, 6 +/- 1 fmol/mg tissue; acutes, 19 +/- 1; and chronics, 16 +/- 1; p = 0.0001) and n. raphe obscurus (SIDS, 28 +/- 3 fmol/mg tissue; acutes, 66 +/- 6; and chronics, 59 +/- 1; p = 0.0001). B inding, however, was also significantly lower (p < 0.05) in 4 other regions that are integral parts of the medullary raphe/serotonergic system, and/or are derived, like the arcuate nucleus and nucleus raphe obscurus, from the same embryonic anlage (rhombic lip). These data suggest that a larger neur onal network than the arcuate nucleus alone is involved in the pathogenesis of SIDS, that is, a network composed of inter-related serotonergic nuclei of the Ventral medulla that are involved in homeostatic mechanisms, and/or are derived from a common embryonic anlage.