期刊
SCIENCE ADVANCES
卷 8, 期 51, 页码 -出版社
AMER ASSOC ADVANCEMENT SCIENCE
DOI: 10.1126/sciadv.add5463
关键词
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资金
- Japan Society for the Promotion of Science [LS070]
- Ministry of Education, Culture, Sports, Science and Technology of Japan [JP21K06767, JP17K08568, JP26860159, JP23790271, JP22K06844, JP22K06470, JP19K06954, JP16K19006, JP21H02592, JP20H03418, JP16H06276, JP16H05128, JP15H05932, JP26118508, JP26713009, JP22689007]
- PRESTO program [JPMJPR13M9]
- FOREST program [JPMJFR204D]
- Moonshot RAMP
- D of the Japan Science and Technology Agency [JPMJMS2024, JPMJMS2023]
- Japan Agency for Medical Research and Development [JP21wm0525002, JP21dm0207112, JP21gm5010002]
- Hori Sciences and Arts Foundation
- Kato Memorial Bioscience Foundation
- Foundation of Kinoshita Memorial Enterprise
- Takeda Science Foundation
- Nakajima Foundation
- Uehara Memorial Foundation
- Ono Medical Research Foundation
- Brain Science Foundation
- Kowa Life Science Foundation
- Nagoya University Research Fund
- Takeda Science Foundation scholarship
- National BioResource Project-Rat, Kyoto University
- Center for Animal Research and Education, Nagoya University
In this study, the bidirectional control of the thermoregulatory center in the preoptic area (POA) was investigated using rats. Prostaglandin EP3 receptor-expressing POA neurons (POAEP3R neurons) were identified as a pivotal bidirectional controller in the central thermoregulatory mechanism. These neurons are activated in response to elevated ambient temperature but inhibited by prostaglandin E2. Stimulation of these neurons reduces body temperature by enhancing heat dissipation, while inhibition of them leads to hyperthermia involving brown fat thermogenesis.
The bidirectional controller of the thermoregulatory center in the preoptic area (POA) is unknown. Using rats, here, we identify prostaglandin EP3 receptor-expressing POA neurons (POAEP3R neurons) as a pivotal bidirec-tional controller in the central thermoregulatory mechanism. POAEP3R neurons are activated in response to el-evated ambient temperature but inhibited by prostaglandin E2, a pyrogenic mediator. Chemogenetic stimulation of POAEP3R neurons at room temperature reduces body temperature by enhancing heat dissipation, whereas inhibition of them elicits hyperthermia involving brown fat thermogenesis, mimicking fever. POAEP3R neurons innervate sympathoexcitatory neurons in the dorsomedial hypothalamus (DMH) via tonic (ceaseless) inhibitory signaling. Although many POAEP3R neuronal cell bodies express a glutamatergic messenger RNA marker, their axons in the DMH predominantly release gamma-aminobutyric acid (GABA), and their GABAergic termi-nals are increased by chronic heat exposure. These findings demonstrate that tonic GABAergic inhibitory sig-naling from POAEP3R neurons is a fundamental determinant of body temperature for thermal homeostasis and fever.
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