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Science. 2016 Sep 23;353(6306):1393-1398. Epub 2016 Aug 25.

The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia.

Author information

1
Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
2
European Molecular Biology Laboratory (EMBL), Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00016 Monterotondo, Italy.
3
European Molecular Biology Laboratory (EMBL), Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00016 Monterotondo, Italy. Molecular Medicine Partnership Unit, EMBL, Meyerhofstraße 1, 69117 Heidelberg, Germany.
4
Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany. Molecular Medicine Partnership Unit, EMBL, Meyerhofstraße 1, 69117 Heidelberg, Germany.

Abstract

Body temperature homeostasis is critical for survival and requires precise regulation by the nervous system. The hypothalamus serves as the principal thermostat that detects and regulates internal temperature. We demonstrate that the ion channel TRPM2 [of the transient receptor potential (TRP) channel family] is a temperature sensor in a subpopulation of hypothalamic neurons. TRPM2 limits the fever response and may detect increased temperatures to prevent overheating. Furthermore, chemogenetic activation and inhibition of hypothalamic TRPM2-expressing neurons in vivo decreased and increased body temperature, respectively. Such manipulation may allow analysis of the beneficial effects of altered body temperature on diverse disease states. Identification of a functional role for TRP channels in monitoring internal body temperature should promote further analysis of molecular mechanisms governing thermoregulation and foster the genetic dissection of hypothalamic circuits involved with temperature homeostasis.

PMID:
27562954
DOI:
10.1126/science.aaf7537
[Indexed for MEDLINE]
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