ONTOGENY OF SOMATOSTATIN BINDING-SITES IN RESPIRATORY NUCLEI OF THE HUMAN BRAIN-STEM

The ontogeny of somatostatin binding sites was studied in 16 respirato ry nuclei of the human brainstem, from 19 postconceptional weeks to 6 months postnatal, by quantitative autoradiography using [I-125-Tyr(0), DTrp(8)]S14 as a radioligand. In the early gestational stages (19-21 p ostconceptional weeks), moderate to high concentrations of [I-125-Tyr( 0),DTrp(8)]S14 binding sites were found in all nuclei, the highest den sity being measured in the locus coeruleus. From 19 weeks of fetal lif e to 6 months postnatal, a decrease in the density of labeling was obs erved in all nuclei. The most dramatic reduction in site density (80-9 0%) was found in the ventral part of the nucleus medullae oblongata la teralis and in the nucleus paragigantocellularis lateralis. A 70-80% d ecrease was detected in the dorsal part of the nucleus tractus solitar ius, the nucleus nervi hypoglossi, the ventral part of the nucleus med ullae oblongatae centralis, the nucleus ambiguus, the nucleus paragiga ntocellularis dorsalis, and the nucleus gigantocellularis, and a 60-70 % decrease in the nucleus parabrachialis medialis, the ventrolateral a nd ventromedial parts of the nucleus tractus solitarius, and the nucle us praepositus hypoglossi. A 50-60% decrease was observed in the cauda l part of the nucleus tractus solitarius, the nucleus dorsalis motoriu s nervi vagi, and the nucleus parabrachialis lateralis, whereas in the nucleus locus coeruleus, the concentration of recognition sites decre ased by only 30%. The profiles of the decrease in site density differe d in the various structures. In the majority of the nuclei, a gradual diminution of binding density was observed either throughout the devel opmental period studied or mainly during fetal life. Conversely, in tw o nuclei, i.e., the nucleus parabrachialis lateralis and the locus coe ruleus, an abrupt decrease occurred around birth. The differential dec rease in the density of somatostatin binding sites observed in respira tory nuclei during development, together with the observation that mic roinjection of somatostatin in some of these nuclei causes ventilatory depression and apnea, strongly suggests that the somatostatinergic sy stems of the human brainstem are involved in the maturation of the res piratory control. (C) 1997 Wiley-Liss, Inc.