liu.seSearch for publications in DiVA
Change search
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf
Immune-Induced Fever Is Dependent on Local But Not Generalized Prostaglandin E-2 Synthesis in the Brain
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Divison of Neurobiology. Linköping University, Faculty of Medicine and Health Sciences.
Linköping University, Department of Clinical and Experimental Medicine, Center for Social and Affective Neuroscience. Linköping University, Faculty of Medicine and Health Sciences.ORCID iD: 0000-0003-2245-3396
Show others and affiliations
2017 (English)In: Journal of Neuroscience, ISSN 0270-6474, E-ISSN 1529-2401, Vol. 37, no 19, 5035-5044 p.Article in journal (Refereed) Published
Abstract [en]

Fever occurs upon binding of prostaglandin E-2 (PGE(2)) to EP3 receptors in the median preoptic nucleus of the hypothalamus, but the origin of the pyrogenic PGE(2) has not been clearly determined. Here, using mice of both sexes, we examined the role of local versus generalized PGE(2) production in the brain for the febrile response. In wild-type mice and in mice with genetic deletion of the prostaglandin synthesizing enzyme cyclooxygenase-2 in the brain endothelium, generated with an inducible CreER(T2) under the Slco1c1 promoter, PGE(2) levels in the CSF were only weakly related to the magnitude of the febrile response, whereas the PGE(2) synthesizing capacity in the hypothalamus, as reflected in the levels of cyclooxygenase-2 mRNA, showed strong correlation with the immune-induced fever. Histological analysis showed that the deletion of cyclooxygenase-2 in brain endothelial cells occurred preferentially in small-and medium-sized vessels deep in the brain parenchyma, such as in the hypothalamus, whereas larger vessels, and particularly those close to the neocortical surface and in the meninges, were left unaffected, hence leaving PGE(2) synthesis largely intact in major parts of the brain while significantly reducing it in the region critical for the febrile response. Furthermore, injection of a virus vector expressing microsomal prostaglandin E synthase-1 (mPGES-1) into the median preoptic nucleus of fever-refractive mPGES-1 knock-out mice, resulted in a temperature elevation in response to LPS. We conclude that the febrile response is dependent on local release of PGE(2) onto its target neurons and not on the overall PGE(2) production in the brain.

Place, publisher, year, edition, pages
SOC NEUROSCIENCE , 2017. Vol. 37, no 19, 5035-5044 p.
Keyword [en]
cyclooxygenase-2; endothelial cells; fever; median preoptic nucleus; microsomal prostaglandin E synthase-1; prostaglandin E2
National Category
Neurosciences
Identifiers
URN: urn:nbn:se:liu:diva-138257DOI: 10.1523/JNEUROSCI.3846-16.2017ISI: 000401118600015PubMedID: 28438967OAI: oai:DiVA.org:liu-138257DiVA: diva2:1109125
Note

Funding Agencies|Swedish Medical Research Council; Swedish Cancer Foundation; European Research Council; Knut and Alice Wallenberg Foundation; Swedish Brain foundation; County Council of Ostergotland

Available from: 2017-06-13 Created: 2017-06-13 Last updated: 2017-06-28

Open Access in DiVA

fulltext(1158 kB)1 downloads
File information
File name FULLTEXT02.pdfFile size 1158 kBChecksum SHA-512
5fd4d02c17c6601be0cfd41013419293bb1ce734b7ae6d6749c9959402099cd84ef548269be49b198de13798df852b7072432b2c52b3b525d27d75a3744215f1
Type fulltextMimetype application/pdf

Other links

Publisher's full textPubMed

Search in DiVA

By author/editor
Eskilsson, AnnaMatsuwaki, TakashiShionoya, KisekoMirrasekhian, ElaheZajdel, JoannaEngblom, DavidBlomqvist, Anders
By organisation
Divison of NeurobiologyFaculty of Medicine and Health SciencesDepartment of Clinical and Experimental MedicineCenter for Social and Affective Neuroscience
In the same journal
Journal of Neuroscience
Neurosciences

Search outside of DiVA

GoogleGoogle Scholar
Total: 1 downloads
The number of downloads is the sum of all downloads of full texts. It may include eg previous versions that are now no longer available

Altmetric score

Total: 811 hits
CiteExportLink to record
Permanent link

Direct link
Cite
Citation style
  • apa
  • harvard1
  • ieee
  • modern-language-association-8th-edition
  • vancouver
  • oxford
  • Other style
More styles
Language
  • de-DE
  • en-GB
  • en-US
  • fi-FI
  • nn-NO
  • nn-NB
  • sv-SE
  • Other locale
More languages
Output format
  • html
  • text
  • asciidoc
  • rtf