Thermoregulation via Temperature-Dependent PGD 2 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.

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