title: TREK-king the blood-brain-barrier.
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.
authors.affiliation: Department of Neurology, University of Münster, Albert-Schweitzer-Campus 1, 48149, Münster, Germany.
authors.forename: Stefan
authors.initials: S
authors.lastname: Bittner
authors.forename: Tobias
authors.initials: T
authors.lastname: Ruck
authors.forename: Juncal
authors.initials: J
authors.lastname: Fernández-Orth
authors.forename: Sven G
authors.initials: SG
authors.lastname: Meuth
mesh_terms: D000818:Animals; D001812:Blood-Brain Barrier / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D002493:Central Nervous System Diseases / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D006801:Humans; D007249:Inflammation / Q000276:immunology / Q000378:metabolism / Q000473:pathology; D051379:Mice; D024683:Potassium Channels, Tandem Pore Domain / Q000276:immunology / Q000378:metabolism*
chemical_list: D024683:Potassium Channels, Tandem Pore Domain; C103742:potassium channel protein TREK-1