Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

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.

Access options

Rent or Buy article

Get time limited or full article access on ReadCube.

from$8.99

All prices are NET prices.

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

References

  1. 1

    Engblom, D. et al. Nat. Neurosci. 6, 1137–1138 (2003).

    CAS  PubMed  Article  Google Scholar 

  2. 2

    Li, S. et al. Brain Res. 825, 86–94 (1999).

    CAS  PubMed  Article  Google Scholar 

  3. 3

    Ek, M. et al. Nature 410, 430–431 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  4. 4

    Scammell, T.E., Griffin, J.D., Elmquist, J.K. & Saper, C.B. Am. J. Physiol. 274, R783–R789 (1998).

    CAS  PubMed  Google Scholar 

  5. 5

    Oka, T. et al. J. Comp. Neurol. 428, 20–32 (2000).

    CAS  PubMed  Article  Google Scholar 

  6. 6

    Ushikubi, F. et al. Nature 395, 281–284 (1998).

    CAS  PubMed  Article  Google Scholar 

  7. 7

    Oka, T. et al. J. Physiol. (Lond.) 551, 945–954 (2003).

    CAS  PubMed Central  Article  Google Scholar 

  8. 8

    Tronche, F. et al. Nat. Genet. 23, 99–103 (1999).

    CAS  PubMed  Article  Google Scholar 

  9. 9

    Morrison, S.F. News Physiol. Sci. 19, 67–74 (2004).

    PubMed  Google Scholar 

  10. 10

    Nakamura, K. et al. J. Neurosci. 22, 4600–4610 (2002).

    CAS  PubMed  Article  Google Scholar 

  11. 11

    Lu, J. et al. J. Neurosci. 21, 4864–4874 (2001).

    CAS  PubMed  PubMed Central  Article  Google Scholar 

  12. 12

    Madden, C.J. & Morrison, S.F. Am. J. Physiol. Regul. Integr. Comp. Physiol. 286, R320–R325 (2004).

    CAS  PubMed  Article  Google Scholar 

  13. 13

    Romanovsky, A.A., Sugimoto, N., Simons, C.T. & Hunter, W.S. Am. J. Physiol. Regul. Integr. Comp. Physiol. 285, R420–R428 (2003).

    CAS  PubMed  Article  Google Scholar 

  14. 14

    Tanaka, M. & McAllen, R.M. Am. J. Physiol. Regul. Integr. Comp. Physiol. 289, R1592–R1598 (2005).

    CAS  PubMed  Article  Google Scholar 

  15. 15

    Oka, T., Oka, K. & Saper, C.B. Brain Res. 968, 256–262 (2003).

    CAS  PubMed  Article  Google Scholar 

Download references

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.

Author information

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.

Ethics declarations

Competing interests

The authors declare no competing financial interests.

Supplementary information

Supplementary Text and Figures

Supplementary Figures 1–3, Methods (PDF 2564 kb)

Rights and permissions

Reprints and Permissions

About this article

Cite this article

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

Download citation

Further reading

Search

Quick links

Nature Briefing

Sign up for the Nature Briefing newsletter — what matters in science, free to your inbox daily.

Get the most important science stories of the day, free in your inbox. Sign up for Nature Briefing