title: Decreased GABAA receptor binding in the medullary serotonergic system in the sudden infant death syndrome.
abstract: γ-Aminobutyric acid (GABA) neurons in the medulla oblongata help regulate homeostasis, in part through interactions with the medullary serotonergic (5-HT) system. Previously, we reported abnormalities in multiple 5-HT markers in the medullary 5-HT system of infants dying from sudden infant death syndrome (SIDS), suggesting that 5-HT dysfunction is involved in its pathogenesis. Here, we tested the hypothesis that markers of GABAA receptors are decreased in the medullary 5-HT system in SIDS cases compared with controls. Using tissue receptor autoradiography with the radioligand H-GABA, we found 25% to 52% reductions in GABAA receptor binding density in 7 of 10 key nuclei sampled of the medullary 5-HT system in the SIDS cases (postconceptional age [PCA] = 51.7 ± 8.3, n = 28) versus age-adjusted controls (PCA = 55.3 ± 13.5, n = 8) (p ≤ 0.04). By Western blotting, there was 46.2% reduction in GABAAα3 subunit levels in the gigantocellularis (component of the medullary 5-HT system) of SIDS cases (PCA = 53.9 ± 8.4, n = 24) versus controls (PCA = 55.3 ± 8.3, n = 8) (56.8% standard in SIDS cases vs 99.35% in controls; p = 0.026). These data suggest that medullary GABAA receptors are abnormal in SIDS infants and that SIDS is a complex disorder of a homeostatic network in the medulla that involves deficits of the GABAergic and 5-HT systems.
authors.affiliation: Department of Pathology, Children's Hospital Boston and Harvard Medical School, Boston, MA 02115, USA. kevin.broadbelt@childrens.harvard.edu
authors.forename: Kevin G
authors.initials: KG
authors.lastname: Broadbelt
authors.forename: David S
authors.initials: DS
authors.lastname: Paterson
authors.forename: Richard A
authors.initials: RA
authors.lastname: Belliveau
authors.forename: Felicia L
authors.initials: FL
authors.lastname: Trachtenberg
authors.forename: Elisabeth A
authors.initials: EA
authors.lastname: Haas
authors.forename: Christina
authors.initials: C
authors.lastname: Stanley
authors.forename: Henry F
authors.initials: HF
authors.lastname: Krous
authors.forename: Hannah C
authors.initials: HC
authors.lastname: Kinney
mesh_terms: D001345:Autoradiography; D005260:Female; D006801:Humans; D007231:Infant, Newborn; D008297:Male; D008526:Medulla Oblongata / Q000378:metabolism*; D011485:Protein Binding / Q000502:physiology; D011963:Receptors, GABA-A / Q000378:metabolism*; D012307:Risk Factors; D012701:Serotonin / Q000378:metabolism*; D013223:Statistics as Topic; D013398:Sudden Infant Death / Q000473:pathology*
chemical_list: D011963:Receptors, GABA-A; D012701:Serotonin