Decreased GABAA Receptor Binding in the Medullary Serotonergic System in the Sudden Infant Death Syndrome

gamma-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 GABA(A) receptors are decreased in the medullary 5-HT system in SIDS cases compared with controls. Using tissue receptor autoradiography with the radioligand H-3-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 GABA(A alpha 3) subunit levels in the gigantocellularis (component of the medullary 5-HT system) of SIDS cases (PCA = 53.9 T 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.