The overall hypothesis of the program project is that the sudden infant death syndrome (SIDS), or a subset of SIDS, is due to developmental abnormalities of the ventral medulla in the brainstem that interfere with normal protective responses to potentially life-threatening, but often occurring, events during sleep, such as hypoxia, hypercapnia, and apnea. Recently we reported neurotransmitter receptor binding deficiencies in SIDS victims in the arcuate nucleus, a region considered homologous to neurons located on the ventral medullary surface in cats that are responsible for the protective responses to hypercapnia and asphyxia. A lesion in the arcuate nucleus could be the only defect in SIDS victims, or a group of SIDS victims. Given the multiple and complex brainstem circuits that underlie protective response to hypoxia, hypercapnia, and apnea, however, a lesion in the arcuate nucleus could be but one of a group of disorders in brainstem protective responses, or alternatively, a central link in a chain of brainstem abnormalities that result in sudden infant death. In this project, we will test the hypothesis that neurotransmitter receptor binding abnormalities in the arcuate nucleus are part of a complex of neurochemical abnormalities in brainstem components related to protective responses to hypoxia, hypercapnia, and apnea.
Our Specific Aims are: 1) To determine if there are neurochemical differences between SIDS and age-matched control brainstems in sites related to protective responses, e.g., in the caudal raphe; and 2) To determine if the putative abnormality in neurotransmitter receptor binding in sites related to protective responses correlate with abnormal 3H-kainate binding to kainate receptors in the arcuate nucleus in the same SIDS cases. Quantitative tissue receptor autoradiography will be used. This project would advance our understanding of the role of the brainstem in the pathogenesis of sudden death in SIDS victims.
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