Thermoregulation via Temperature-Dependent PGD2 Production in Mouse Preoptic Area

Tongfei A Wang; Chin Fen Teo; Malin Åkerblom; Chao Chen; Marena Tynan-La Fontaine; Vanille Juliette Greiner; Aaron Diaz; Michael T McManus; Yuh Nung Jan; Lily Y Jan

doi:10.1016/j.neuron.2019.04.035

Thermoregulation via Temperature-Dependent PGD₂ Production in Mouse Preoptic Area

Neuron. 2019 Jul 17;103(2):309-322.e7. doi: 10.1016/j.neuron.2019.04.035. Epub 2019 May 28.

Affiliations

¹ Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA.
² Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA.
³ Department of Microbiology and Immunology, University of California, San Francisco, San Francisco, CA 94158, USA; UCSF Diabetes Center, University of California, San Francisco, San Francisco, CA 94158, USA.
⁴ Department of Neurological Surgery, University of California, San Francisco, San Francisco, CA 94158, USA.
⁵ Departments of Physiology, Biochemistry and Biophysics, University of California, San Francisco, San Francisco, CA 94158, USA; Howard Hughes Medical Institute, University of California, San Francisco, San Francisco, CA 94158, USA. Electronic address: lily.jan@ucsf.edu.

Abstract

Body temperature control is essential for survival. In mammals, thermoregulation is mediated by the preoptic area of anterior hypothalamus (POA), with ∼30% of its neurons sensitive to brain temperature change. It is still unknown whether and how these temperature-sensitive neurons are involved in thermoregulation, because for eight decades they have only been identified via electrophysiological recording. By combining single-cell RNA-seq with whole-cell patch-clamp recordings, we identified Ptgds as a genetic marker for temperature-sensitive POA neurons. Then, we demonstrated these neurons' role in thermoregulation via chemogenetics. Given that Ptgds encodes the enzyme that synthesizes prostaglandin D2 (PGD₂), we further explored its role in thermoregulation. Our study revealed that rising temperature of POA alters the activity of Ptgds-expressing neurons so as to increase PGD₂ production. PGD₂ activates its receptor DP1 and excites downstream neurons in the ventral medial preoptic area (vMPO) that mediates body temperature decrease, a negative feedback loop for thermoregulation.

Publication types

Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

MeSH terms

Action Potentials / drug effects
Action Potentials / physiology
Animals
Body Temperature / drug effects
Body Temperature / physiology
Body Temperature Regulation / genetics
Body Temperature Regulation / physiology*
CRISPR-Associated Protein 9 / genetics
CRISPR-Associated Protein 9 / metabolism
Clozapine / pharmacology
Dinoprostone / genetics
Dinoprostone / metabolism
Excitatory Amino Acid Antagonists / pharmacology
Gene Expression Regulation / genetics
HEK293 Cells
Humans
Locomotion / drug effects
Locomotion / genetics
Male
Mice
Mice, Inbred C57BL
Mice, Transgenic
Neurons / drug effects
Neurons / physiology*
Preoptic Area / cytology*
Preoptic Area / drug effects
Preoptic Area / physiology*
Prostaglandin D2 / genetics
Prostaglandin D2 / metabolism*
Temperature*

Substances

Excitatory Amino Acid Antagonists
CRISPR-Associated Protein 9
Clozapine
Dinoprostone
Prostaglandin D2