TY  - JOUR
A1  - Bittner, Stefan
A1  - Bobak, Nicole
A1  - Hofmann, Majella-Sophie
A1  - Schuhmann, Michael K.
A1  - Ruck, Tobias
A1  - Göbel, Kerstin
A1  - Brück, Wolfgang
A1  - Wiendl, Heinz
A1  - Meuth, Sven G.
T1  - Murine K\(_{2P}\)5.1 Deficiency Has No Impact on Autoimmune Neuroinflammation due to Compensatory K\(_{2P}\)3.1-and K\(_{V}\)1.3-Dependent Mechanisms
JF  - International Journal of Molecular Sciences
N2  - Lymphocytes express potassium channels that regulate physiological cell functions, such as activation, proliferation and migration. Expression levels of K\(_{2P}\)5.1(TASK2; KCNK5) channels belonging to the family of two-pore domain potassium channels have previously been correlated to the activity of autoreactive T lymphocytes in patients with multiple sclerosis and rheumatoid arthritis. In humans, K\(_{2P}\)5.1 channels are upregulated upon T cell stimulation and influence T cell effector functions. However, a further clinical translation of targeting K\(_{2P}\)5.1 is currently hampered by a lack of highly selective inhibitors, making it necessary to evaluate the impact of KCNK5 in established preclinical animal disease models. We here demonstrate that K\(_{2P}\)5.1 knockout (K\(_{2P}\)5.1\(^{-/-}\) mice display no significant alterations concerning T cell cytokine production, proliferation rates, surface marker molecules or signaling pathways. In an experimental model of autoimmune neuroinflammation, K\(_{2P}\)5.1\(^{-/-}\) mice show a comparable disease course to wild-type animals and no major changes in the peripheral immune system or CNS compartment. A compensatory upregulation of the potassium channels K\(_{2P}\)3.1 and K\(_{V}\)1.3 seems to counterbalance the deletion of K\(_{2P}\)5.1. As an alternative model mimicking autoimmune neuroinflammation, experimental autoimmune encephalomyelitis in the common marmoset has been proposed, especially for testing the efficacy of new potential drugs. Initial experiments show that K\(_{2P}\)5.1 is functionally expressed on marmoset T lymphocytes, opening up the possibility for assessing future K\(_{2P}\)5.1-targeting drugs.
KW  - domain potassium channels
KW  - volume regulation
KW  - multiple-sclerosis
KW  - potassium channels
KW  - multiple sclerosis
KW  - ion channels
KW  - K+ channel
KW  - T lymphocytes
KW  - up-regulation
KW  - TASK2
KW  - K2P channels
KW  - B cells
KW  - ph
KW  - K\(_{2P}\)5.1
KW  - KCNK5
KW  - autoimmune neuroinflammation
KW  - EAE
Y1  - 2015
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-151454
VL  - 16
SP  - 16880
EP  - 16896
ER  - 
TY  - JOUR
A1  - Brandt, Alexander U.
A1  - Zimmermann, Hanna
A1  - Kaufhold, Falko
A1  - Promesberger, Julia
A1  - Schippling, Sven
A1  - Finis, David
A1  - Aktas, Orhan
A1  - Geis, Christian
A1  - Ringelstein, Marius
A1  - Ringelstein, E. Bernd
A1  - Hartung, Hans-Peter
A1  - Paul, Friedemann
A1  - Kleffner, Ilka
A1  - Dörr, Jan
T1  - Patterns of Retinal Damage Facilitate Differential Diagnosis between Susac Syndrome and MS
JF  - PLoS One
N2  - Susac syndrome, a rare but probably underdiagnosed combination of encephalopathy, hearing loss, and visual deficits due to branch retinal artery occlusion of unknown aetiology has to be considered as differential diagnosis in various conditions. Particularly, differentiation from multiple sclerosis is often challenging since both clinical presentation and diagnostic findings may overlap. Optical coherence tomography is a powerful and easy to perform diagnostic tool to analyse the morphological integrity of retinal structures and is increasingly established to depict characteristic patterns of retinal pathology in multiple sclerosis. Against this background we hypothesised that differential patterns of retinal pathology facilitate a reliable differentiation between Susac syndrome and multiple sclerosis. In this multicenter cross-sectional observational study optical coherence tomography was performed in nine patients with a definite diagnosis of Susac syndrome. Data were compared with age-, sex-, and disease duration-matched relapsing remitting multiple sclerosis patients with and without a history of optic neuritis, and with healthy controls. Using generalised estimating equation models, Susac patients showed a significant reduction in either or both retinal nerve fibre layer thickness and total macular volume in comparison to both healthy controls and relapsing remitting multiple sclerosis patients. However, in contrast to the multiple sclerosis patients this reduction was not distributed over the entire scanning area but showed a distinct sectorial loss especially in the macular measurements. We therefore conclude that patients with Susac syndrome show distinct abnormalities in optical coherence tomography in comparison to multiple sclerosis patients. These findings recommend optical coherence tomography as a promising tool for differentiating Susac syndrome from MS.
KW  - optical coherence tomography
KW  - vasculopathy
KW  - artery occlusion
KW  - hearing loss
KW  - microangiopathy
KW  - brain
KW  - endotheliopathy
KW  - antibodies
KW  - multiple-sclerosis
KW  - retinocochleocerebral
Y1  - 2012
U6  - http://nbn-resolving.de/urn/resolver.pl?urn:nbn:de:bvb:20-opus-134013
VL  - 7
IS  - 6
ER  -