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Journal of Neuroimmune Pharmacology

, Volume 9, Issue 3, pp 293–301 | Cite as

TREK-King the Blood–Brain-Barrier

  • Stefan Bittner
  • Tobias Ruck
  • Juncal Fernández-Orth
  • Sven G. Meuth
PERSPECTIVE

Abstract

TWIK-related potassium channel-1 (TREK1, KCNK2) is the most extensively studied member of the two-pore domain potassium (K2P) channel family. Recent studies have already demonstrated a key role in the pathophysiology of depression, pain and neurodegenerative damage pointing towards an important role in a broad spectrum of CNS disorders. The mammalian blood–brain barrier (BBB) is a highly specialized structure and an integral part of the neurovascular unit, which controls the transition of cells and molecules into the CNS. While BBB dysregulation is common in neurologic diseases, the molecular mechanisms involved in this process remain largely unknown. Recently, we were able to describe a role of TREK1 in this context. TREK1 was downregulated in murine and human BBB upon inflammation. Blocking of TREK1 increased lymphocyte migration, while activation had the opposite effect. In TREK1-deficient (Trek1 −/− ) mice, brain endothelial cells displayed an inflammatory phenotype and leukocyte trafficking was facilitated, as demonstrated in experimental autoimmune encephalomyelitis (EAE), an animal model for multiple sclerosis. Here we summarize these findings and discuss the implications in diseases related to BBB dysfunction.

Keywords

Multiple Sclerosis Ion channels K2P channels TREK1 Blood–brain barrier Neuroinflammation 

Notes

Acknowledgments

This work was supported by the Deutsche Forschungsgemeinschaft (SFB TR128, TP B6 to S.G.M., FOR1086, TP2 to S.G.M. and ME3283/2-1 to S.G.M.), the Else-Kröner-Fresenius Stiftung (S.B., S.G.M.), the Interdisciplinary Center for Clinical Research (IZKF) Münster (SEED 03/12 to S.B.) and the excellence cluster ‘Cells in motion’ (CIM, to S.G.M., H.W., S.B.).

Disclosure

The authors have no conflicts of interest or financial disclosures to make.

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Copyright information

© Springer Science+Business Media New York 2014

Authors and Affiliations

  • Stefan Bittner
    • 1
    • 2
  • Tobias Ruck
    • 1
  • Juncal Fernández-Orth
    • 1
  • Sven G. Meuth
    • 1
    • 3
  1. 1.Department of NeurologyUniversity of MünsterMünsterGermany
  2. 2.Interdisciplinary Center for Clinical Research (IZKF)MünsterGermany
  3. 3.Institute of Physiology I – NeuropathophysiologyUniversity of MünsterMünsterGermany

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