Prothrombin overexpressed in post-natal neurones requires blood factors for activation in the mouse brain

Michael Sinnreich, Marita Meins, Simone P. Niclou, Hana S. Suidan, Denis Monard*

*Corresponding author for this work

Research output: Contribution to journalArticleResearchpeer-review

13 Citations (Scopus)

Abstract

Thrombin is thought to mediate, through protease-activated receptors, both protective as well as cytotoxic effects. As thrombin receptors are expressed in the CNS, an important question arises as to whether the intact nervous system is able to generate thrombin by activation of its precursor prothrombin, derived endogenously or only upon extravasation following brain injury. To address this question, transgenic mice that express C-terminally haemagglutinin tagged human prothrombin in post-mitotic neurones were generated. In situ hybridization and immunohistochemical analysis showed abundant and widespread cerebral expression of the transgene. Amidolytic assays of brain homogenates and hippocampal slice cultures demonstrated that activation of transgenic prothrombin required added factors, such as snake venom or blood components. This strongly suggests that any possible action of thrombin in the adult CNS depends on blood-derived factors that activate prothrombin. Furthermore, the results are consistent with the idea that in the nonpathological situation an as yet unidentified ligand activates thrombin receptors in the nervous system.

Original languageEnglish
Pages (from-to)1380-1388
Number of pages9
JournalJournal of Neurochemistry
Volume88
Issue number6
DOIs
Publication statusPublished - Mar 2004
Externally publishedYes

Keywords

  • Brain
  • Protease-activated receptor-1
  • Prothrombin
  • Thrombin
  • Thrombin receptor
  • Transgenic mice

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