title: The TRPM2 channel is a hypothalamic heat sensor that limits fever and can drive hypothermia.
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.
authors: Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors: Kun
authors: K
authors: Song
authors: Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors: Hong
authors: H
authors: Wang
authors: Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors: Gretel B
authors: GB
authors: Kamm
authors: Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors: Jörg
authors: J
authors: Pohle
authors: European Molecular Biology Laboratory (EMBL), Adriano Buzzati-Traverso Campus, Via Ramarini 32, 00016 Monterotondo, Italy.
authors: Fernanda de Castro
authors: FC
authors: Reis
authors: 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.
authors: Paul
authors: P
authors: Heppenstall
authors: Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany.
authors: Hagen
authors: H
authors: Wende
authors: Department of Pharmacology, University of Heidelberg, Im Neuenheimer Feld 366, 69120 Heidelberg, Germany. Molecular Medicine Partnership Unit, EMBL, Meyerhofstraße 1, 69117 Heidelberg, Germany.
authors: Jan
authors: J
authors: Siemens
mesh_terms: D000818:Animals; D001833:Body Temperature Regulation / Q000235:genetics / Q000502:physiology*; D005260:Female; D005334:Fever / Q000235:genetics / Q000503:physiopathology*; D006358:Hot Temperature; D007035:Hypothermia / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D008817:Mice, Mutant Strains; D009474:Neurons / Q000502:physiology; D011301:Preoptic Area / Q000166:cytology / Q000502:physiology*; D050053:TRPM Cation Channels / Q000235:genetics / Q000502:physiology*
chemical_list: D050053:TRPM Cation Channels; C544443:TRPM2 protein, mouse