Prostaglandin EP3 receptor‐expressing neurons in the preoptic area are activated by ambient heat exposure

Abstract

The preoptic area (POA) receives cutaneous warm and cold inputs ascending through the lateral parabrachial nucleus, and local neural circuits in the POA function as a center for body temperature regulation. The cutaneous warm inputs to the POA can activate inhibitory neurons therein, which then inhibit the sympathoexcitatory efferent neural pathways that otherwise drive cold‐defensive thermogenesis and cutaneous vasoconstriction. The POA also contains warm‐sensitive neurons that have intrinsic warm sensitivity to monitor body core (local brain tissue) temperature and thereby determine the basal tone of the thermoregulatory efferent signaling, although the histochemical or molecular identity of warm‐sensitive neurons remains unknown. The prostaglandin EP3 receptor, a Gi‐coupled inhibitory receptor of prostaglandin E2, a pyrogenic mediator, is expressed in POA neurons, and an action of prostaglandin E2 on these neurons triggers fever likely by disinhibiting sympathoexcitatory neurons in the dorsomedial hypothalamus and the rostral medullary raphe region. To determine whether EP3 receptor‐expressing POA neurons contribute to thermal homeostasis in warm and cold conditions, in this study, we exposed rats to a heated (36°C), control (24°C) or cold (4°C) environment for two hours and examined activation of EP3 receptor‐expressing POA neurons by double‐immunostaining for EP3 receptors and c‐Fos, a marker for neuronal activation. Heat‐exposed rats exhibited a significant increase in c‐Fos‐positive cells in EP3 receptor‐expressing POA neurons, compared with rats exposed to the control environment. However, cold exposure had no significant effect on the number of c‐Fos‐positive cells in EP3 receptor‐expressing POA neurons, compared with control exposure. These results suggest that EP3 receptor‐expressing POA neurons are activated in hot environments due to its intrinsic warm sensitivity and/or by cutaneous warm inputs and function for heat defense, as well as fever development after infection.Support or Funding InformationJSPS KAKENHI 17K08568, 23790271 & 26860159 (YN), 16H05128, 15H05932 & 26118508 (KN); AMED JP18gm5010002 (KN); Hori Sciences and Arts Foundation (YN)This abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.