美国哈佛医学院Clifford B. Saper团队的一项最新研究发现了视前EP3R神经元构成发烧和麻木的双向开关。相关论文于2025年5月28日发表在《自然》杂志上。

在这里，课题组报道了前列腺素EP3受体（EP3R）的表达标志着一个独特的中位视前核细胞（MnPO）神经元群，这是麻木和脂多糖诱导的发烧所必需的。MnPO-EP3R神经元在受到抑制时产生持续的发热反应，而在化学遗传学或光遗传学激活时，即使是很短的时间，也会产生持续的低温反应。这些延长反应的机制似乎与细胞内cAMP和钙水平的增加有关，这种增加可能在刺激终止后持续数分钟至数小时。这些特性赋予了MnPO-EP3R神经元群体作为生存所需的低温和高温反应的双向开关的能力。

据介绍，许多物种将体温和代谢率的暂时降低（冬眠）作为在寒冷环境中食物短缺的生存策略。冬眠由表达多种多肽和受体的视前神经元组成，但尚未发现该群体的单一遗传标记。

附：英文原文

Title: Preoptic EP3R neurons constitute a two-way switch for fever and torpor

Author: Machado, Natalia L. S., Lynch, Nicole, Costa, Luis H. A., Melville, David, Kucukdereli, Hakan, Kaur, Satvinder, Banks, Alexander S., Raffin, Francesca, Ramirez-Plascencia, Oscar D., Aten, Sydney, Lima, Janayna D., Bandaru, Sathyajit S., Palmiter, Richard D., Saper, Clifford B.

Issue&Volume: 2025-05-28

Abstract: Many species use a temporary decrease in body temperature and metabolic rate (torpor) as a strategy to survive food scarcity in a cool environment. Torpor is caused by preoptic neurons that express a variety of peptides and receptors1,2,3,4,5,6,7, but no single genetic marker has been found for this population. Here we report that expression of the prostaglandin EP3 receptor (EP3R) marks a unique population of median preoptic nucleus (MnPO) neurons that are required for both torpor and lipopolysaccharide-induced fever8. The MnPO-EP3R neurons produce persistent fever responses when inhibited and prolonged hypothermic responses when activated either chemogenetically or optogenetically, even for brief periods of time. The mechanism for these prolonged responses appears to involve increases in intracellular levels of cAMP and calcium that may persist for many minutes up to hours beyond the termination of a stimulus. These properties endow the population of MnPO-EP3R neurons with the ability to act as a two-way switch for the hypothermic and hyperthermic responses that are required for survival.

DOI: 10.1038/s41586-025-09056-1

Source: https://www.nature.com/articles/s41586-025-09056-1