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

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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.
Total Authors: 14
Document type: Journal article
Source: Nature; v. N/A, p. 26-pg., 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. (AU)

FAPESP's process: 22/12780-0 - Hypothermia as a therapeutic strategy for ischemic stroke
Grantee:Luís Henrique Angenendt da Costa
Support Opportunities: Scholarships abroad - Research Internship - Post-doctor