Distribution of 5‐HT2A receptors in the human infant medulla

Abstract

The 5-HT system in the medulla oblongata plays an important role in the regulation of homeostatic function. Previously, we identified multiple 5-HT abnormalities in the medulla in SIDS infants, including a significant reduction in 5-HT1A receptor binding. The question remains whether the expression of other 5-HT receptor subtypes are abnormal in SIDS. As a first step towards answering this question, we mapped the distribution of the 5-HT2A receptor in normative human infant medulla using tissue section autoradiography with 86.3pM 125I DOI (n=5) and immunocytochemistry with goat polyclonal antibody at a 1:100 dilution (n=4). The 5-HT2A receptor plays important roles in 5-HT-mediated cardiorespiratory functions in animals, including firing of preBötzinger Complex neurons. High 5-HT2A receptor binding was observed in the dorsal motor nucleus of the vagus, hypoglossal nucleus and olivary complex; intermediate binding was present in the nucleus of the solitary tract and paragigantocellularis lateralis; low binding was detected in the arcuate nucleus and raphé. The pattern of 5-HT2A immunostaining was consistent with that of binding. These observations indicate that 5-HT2A receptors localize to medullary regions concerned with cardiorespiratory function in the human infant, and underscore their importance in the analysis of the medullary 5-HT hypothesis in SIDS. Support: NICHD (R37-HD20991, PO1-HD36379), CJ Murphy Foundation