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