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EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses

Abstract

Fever is a result of the action of prostaglandin E2 (PGE2) on the brain and appears to require EP3 prostaglandin receptors (EP3Rs), but the specific neurons on which PGE2 acts to produce fever have not been definitively established. Here we report that selective genetic deletion of the EP3Rs in the median preoptic nucleus of mice resulted in abrogation of the fever response. These observations demonstrate that the EP3R-bearing neurons in the median preoptic nucleus are required for fever responses.

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Figure 1: Generation of conditional EP3R mice.
Figure 2: Site-specific deletion of EP3 receptors in the MnPO.

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Acknowledgements

We would like to thank Q. Ha, M. Ha and J. Yu for superb technical assistance and J. Lu, N.L. Chamberlin, J.K. Elmquist and O. Hayaishi for critical reading of the manuscript and valuable comments. This research was supported by US Public Health Service grants NS33987 and HL60292.

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Authors and Affiliations

Authors

Contributions

M.L. was responsible for all phases of the experimental work, performing the analyses and writing of the manuscript. K.Y. participated in the physiological recording and histology. R.C. and B.B.L. assisted with design and execution of preparing the genetically altered mice. C.E.B. assisted with the design and production of the AAV-Cre vectors. T.M. assisted with physiological recordings. C.B.S. was responsible for overall design of the project and analysis of results, and edited the manuscript.

Corresponding author

Correspondence to Clifford B Saper.

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The authors declare no competing financial interests.

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Lazarus, M., Yoshida, K., Coppari, R. et al. EP3 prostaglandin receptors in the median preoptic nucleus are critical for fever responses. Nat Neurosci 10, 1131–1133 (2007). https://doi.org/10.1038/nn1949

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