Differential development of 5‐HT receptor and the serotonin transporter binding in the human infant medulla

Abstract

Tissue receptor autoradiography with 3H-lysergic acid diethylamide (3H-LSD), 3H-8-hydroxy-2-[di-N-propylamine] tetralin (3H-8-OH-DPAT), and 125I-RTI-55 was used to map the distribution and developmental profile of 5-HT(1A-1D) and 5-HT2 receptors, 5-HT1A receptors, and the serotonin (5-HT) transporter (SERT), respectively, to nuclei with cardiorespiratory function in the human medulla from midgestation to maturity. The distribution pattern of the 5-HT markers was heterogeneous, with variable densities of binding of each observed both in nuclei with and without 5-HT cell bodies. The highest density of binding for each marker was observed in the raphé nuclei, the site of the highest density of 5-HT cell bodies. A significant reduction in 5-HT receptor binding measured with 3H-LSD was observed between midgestation and infancy, and between infancy and maturity in multiple nuclei, but no changes were observed across infancy. A significant increase in 5-HT1A receptor binding density was observed across infancy in the hypoglossal nucleus (regression slope coefficient = 0.008 +/- 0.002, P = 0.02), and a marginally significant increase was observed in the raphé obscurus (regression slope coefficient = 0.061 +/- 0.026 [mean +/- SEM], P = 0.05). No significant age-related changes in SERT binding were observed at any time. With the exception of the hypoglossal nucleus, where 5-HT1A receptor binding increases while SERT binding remains stable, the medullary 5-HT markers analyzed in the study are essentially "in place" at birth. This study provides important baseline data that serve as a foundation for future work in pediatric 5-HT brainstem disorders, including sudden infant death syndrome.

Decreased GABAAReceptor Binding in the Medullary Serotonergic System in the Sudden Infant Death Syndrome

“…In Stage 1, film autoradiograms were generated according to standard laboratory procedure for development of light sensitive film (38); in Stage 2, imaging plates were read and imaged using a BAS-5000 Phosphoimager (Fuji Biosystems), then exported to a computerized system (MCID Elite 6; Imaging Research Inc, Mississauga, ONT, Canada) for densitometry quantification (10). For each specimen, receptor-binding density was analyzed in 10 medullary nuclei at defined levels (see below) of the brainstem (2 autoradiograms/nucleus), as previously described (7–10, 38, 40). …”

Early postnatal stress alters the 5-HTergic modulation to emotional stress at postadolescent periods of rats

“…Numerous animal studies have provided evidence that serotonin (5-HT) in the limbic system is involved in the regulation of emotional stress (Yoshioka et al, 1995;Rueter et al, 1996;Roche et al, 2003). Recent studies focus on the development of the 5-HTergic systems in the forebrain during early postnatal periods Paterson et al, 2004). Early postnatal stresses are also known to alter the 5-HTergic systems by regulating 5-HT receptors.…”

Multiple Serotonergic Brainstem Abnormalities in Sudden Infant Death Syndrome

“…For each specimen, receptor or transporter binding density was analyzed in 9 medullary nuclei (all nuclei were not available in all cases) at a defined level of the brainstem (2 autoradiograms for each nucleus) according to previously published methods. 9,22,38 Quantitative densitometry of autoradiograms was performed using an MCID 5ϩ imaging system (Imaging Research Inc, St Catharines, Ontario).…”