Prof. Dr. Klaus Reymann
Group Leader
German Center for Neurodegenerative Diseases (DZNE)
Brenneckestr. 6
39118 Magdeburg
klaus.reymann(at)dzne.de
+49 (0) 391 / 6263-93431
+49 (0) 391 / 6263 93439
More information
Areas of investigation/research focus
Our preclinical research team has started to settle new models and research tools in collaboration with the Leibniz Institute for Neurobiology Magdeburg and the Clinic for Neurology Magdeburg and will focus on neuroprotective and compensatory strategies against dementia as well as diagnostic imaging tools using animals and tissue cultures.
Deep brain stimulation
Alzheimer’s disease is associated with a decline of cognitive functions such as memory lost. With the 5xFAD- tg6799 mice we have established fear conditioning and shuttle box learning as an animal models for this disease. We work on strategies for therapeutic compensation of memory decline boosting the dopamine mechanisms by deep brain stimulation or dopamine agonist treatment. We now stimulate reward centres, especially the dopaminergic ventral tegmental area and the medial forebrain bundle, of the brain to improve memory function. If memory improvements can be obtained, we will analyze the underlying mechanisms like network plasticity and neurogenesis.
- Setup for VTA-stimulation in cognitive impaired mice
Pharmacology of amyloid ß-induced functional disturbances
The disturbances of neuronal function induced by sublethal Aβ concentrations are hypothesized to be the first stages of the cognitive decline in patients. We investigate the mechanisms and related drug targets of amyloid ß-induced functional disturbances. It is known that Aß oligomerization leads to the impairment of long-term potentiation, a form of synaptic memory. We found out that Aß oligomers cause also decreased neuronal spontaneous network activity and spine retraction long before cytotoxic effects are visible (collaboration with Georg Reiser, Neurobiochemistry Magdeburg). The Aβ-mediated neuronal dysfunction can be blocked with the NR2B containing NMDA-receptor antagonists like ifenprodil suggesting that activation of downstream effectors of these receptors is involved in early detrimental actions of Aβ oligomers. In line we found that Jacob, a messenger that can couple extrasynaptic NMDA-receptor activity to CREB dephosphorylation, accumulates in the nucleus of pyramidal cells after Aβ oligomer administration (collaboration with Michael Kreutz, Neurobiology Magdeburg). In the meanwhile we use hippoacmpal LTP as a model for testing several AD drug candidates. Additionally we investigate into the question whether chronically elevated Ab levels affect the molecular compositions of pre- and postsynaptic specializations (in collaboration with Dr. Fejtová and Prof. Gundelfinger, Neurobiology Magdeburg).
- The NMDAR-2B antagonist ifenprodil restores the LTP-impairment after oligomeric Aβ
- Aß-amyloid reduces the spontaneous neuronbal activity in a primayry neuronal culture (Fura-imaging).
Mechanisms of vascular and mixed dementia
In future our research will focus on finding neuroprotective strategies against vascular and mixed dementia. Vascular dementia remains the second most common cause of age-related dementia. It may result from all forms of cerebrovascular injury, which sometimes may include post-stroke syndromes. The challenge of defining the pathological substrates of vascular dementia is complicated by the heterogeneous nature of cerebrovascular disease and coexistence of other pathologies including Alzheimer type of lesions. To describe the pathophysiology of vascular dementia we study changes in vessels in animal models with magnetic resonance imaging and two-photon imaging. We try to develop new animal models and want to study mechanisms of interaction between the nervous and the immune system. We have started to describe the natural pathophysiology of cerebral small vessel disease (SVD) in SHSP rats without feeding a salt-loaded diet. SVD starts long before pathognomonic changes including microbleeds and microthromboses occur (together with Michael Görtler, Neurology Magdeburg).
Imaging of dementia in transgenic mice
Together with Jürgen Goldschmidt and Henning Scheich (Neurobiology Magdeburg) we are developing new tools for analyzing pathological network dysfunction as well as diagnostic imaging. We are comparing AD-mutants with non-transgenic littermates for their patterns of neuronal activity during normal behaviour. For that, we are mapping neuronal activity by thallium autometallography. The method is based on the tight coupling of neuronal activity and potassium uptake. Potassium-analogues like the heavy metal ion thallium can be used as tracers for imaging neuronal activity. In addition, we establish SPECT analysis of neuronal activity with 201-Thallium and 99-Technitium, which could be appropriate to demonstrate Alzheimer-related change of activity patterns and could serve, therefore, as a tracer for early Alzheimer-diagnosis.
- Thallium and blood flow markers also allow to dissect activated of brain areas following electrically stimulation of reward pathways.The figure shows on the left a high resolution anatomical MRI of the mouse head with a stimulation electrode in a reward pathway (medial forebrain bundle - arrow). On the right the electrically activated brain areas (yellow) in the SPECT imaging are superimposed.
Publications
N-Terminal pyroglutamate formation of Aβ38 and Aβ40 enforces oligomer formation and potency to disrupt hippocampal long-term potentiation.
Schlenzig D, Rönicke R, Cynis H, Ludwig HH, Scheel E, Reymann K, Saido T, Hause G, Schilling S, Demuth HU. J Neurochem. 2012 Jun;121(5):774-84. doi: 10.1111/j.1471-4159.2012.07707.x. Epub 2012 Mar 28.
Structural basis of β-amyloid-dependent synaptic dysfunctions.
Haupt C, Leppert J, Rönicke R, Meinhardt J, Yadav JK, Ramachandran R, Ohlenschläger O, Reymann KG, Görlach M, Fändrich M. Angew Chem Int Ed Engl. 2012 Feb 13;51(7):1576-9. doi: 10.1002/anie.201105638. Epub 2012 Jan 10.
The pathologic cascade of cerebrovascular lesions in SHRSP: is erythrocyte accumulation an early phase?
S Schreiber, CZ Bueche, C Garz, S Kropf, F Angenstein, J Goldschmidt, J Neumann, HJ Heinze, M Goertler, KG Reymann, H Braun; J Cereb Blood Flow Metab. 2012 Feb;32(2):278-90. doi: 10.1038/jcbfm.2011.122. Epub 2011 Aug 31.
Insufficient endogenous redox buffer capacity may underlie neuronal vulnerability to cerebral ischemia and reperfusion.
P Röhnert, UH Schröder, I Ziabreva, M Täger, KG Reymann, F Striggow; J Neurosci Res. 2012 Jan;90(1):193-202. doi: 10.1002/jnr.22754. Epub 2011 Oct 4.
Post-translational membrane insertion of tail-anchored transmembrane EF-hand Ca2+ sensor calneurons requires the TRC40/Asna1 protein chaperone
J Hradsky, V Raghuram, PP Reddy, G Navarro, M Hupe, V Casado, PJ McCormick, Y Sharma, MR Kreutz, M Mikhaylova; J Biol Chem. 2011 Oct 21;286(42):36762-76. Epub 2011 Aug 30.
Kidney pathology precedes and predicts the pathological cascade of cerebrovascular lesions in stroke prone rats.
S Schreiber, CZ Bueche, C Garz, S Kropf, D Kuester, K Amann, HJ Heinze, M Goertler, KG Reymann, H Braun; PLoS One. 2011;6(10):e26287. Epub 2011 Oct 21.
Effects of transient global ischaemia on freezing behaviour and activity in a context-dependent fear conditioning task - Implications for memory investigations.
P Henrich-Noack, K Krautwald, KG Reymann, W Wetzel, Brain Research Bulletin, 2011 Jul 15, 85(6), pp. 346-353.
Combining independent drug classes into superior, synergistically acting hybrid molecules.
Müller-Schiffmann, A., März, J., Andreyeva, A., Rönicke, R., Bartnik, D., Brener, O., Muyrers, J., Horn, A.H.C., Gottmann, K., Reymann, K., Funke, S.A., Nagel-Steger, L., Moriscot, C., Schoehn, G., Sticht, H., Willbold, D., Schrader, T., and Korth, C., Angew. Chem. Int. Ed. Engl,. 2010, 49:8743-6.
Functional interaction of metabotropic glutamate receptor 5 (mGluR5) and NMDA-receptor by an mGluR5 positive allosteric modulator in-vitro and in-vivo.
Rosenbrock, H, Kramer, G., Hobson, S, Koros, E, Grundl, M, Grauert, M, Reymann, KG and Schröder, UH., Eur. J. Pharmacol. , 2010, 639: 40-46.
Early neuronal dysfunction by amyloid beta oligomers depends on activation of NR2B-containing NMDA receptors.
Rönicke R, Mikhaylova M, Rönicke S, Meinhardt J, Schröder UH, Fändrich M, Reiser G, Kreutz MR, Reymann KG., Neurobiol Aging. 2010 (Epub ahead of print)
Inhibition of calpain prevents NMDA-induced cell death and beta-amyloid-induced synaptic dysfunction in hippocampal slice cultures.
Nimmrich V, Reymann KG, Strassburger M, Schöder UH, Gross G, Hahn A, Schoemaker H, Wicke K, Möller A., Br J Pharmacol. 2010, 159:1523-1531
Mechanism of amyloid plaque formation suggests an intracellular basis of Aβ pathogenicity.
Friedrich RP, Tepper K, Rönicke R, Soom M, Westermann M, Reymann K, Kaether C, Fändrich M., Proc Natl Acad Sci U S A, 2010, 107, 1942-1947
Cellular expression pattern of the protease-activated receptor 4 in the hippocampal CA3/CA4 area in naïve rats and after global ischaemia.
Henrich-Noack, P., Riek-Burchardt, M., Reymann, K.G., and Reiser, G., J. Neurosci. Res., 2010, 88, 850-857.
Differential regulation of CXCL12 and PACAP mRNA expression after focal and global ischemia.
Riek-Burchardt, M., Kolodziej, A, Henrich-Noack, P., Reymann, K.G., Höllt, V., and Stumm, R., Neuropharmacology, 2010, 58, 199-207
Neuroprotective effects of the survival promoting peptide Y-P30.
Schneeberg, J., Riek-Burchardt, M., Braun, H., Landgraf, P., Kreutz, M.R., and Reymann, K.G., Eur. J. Pharmacol. 2009, 616, 81-85.
The Neuroprotective effect of bone marrow stem cells is not dependent on direct cell contact with hypoxic injured tissue.
Sarnowska, A., Braun, H, Sauerzweig, S. and Reymann, K.G., Exp. Neurol., 2009, 215, 317-327
Degradation and translocalization of incorporated BrdU leads to fragmented labeled nuclei and false negative results.
Sauerzweig, S., Baldauf, K., Braun, H. and Reymann, K.G., J. Neurosci. Meth., 2009, 177, 149-59
A population of serum deprivation-induced bone marrow stem cells (SD-BMSC) expresses marker typical for embryonic and neural stem cells.
Sauerzweig, S. Munsch, T., Leßmann, V., Reymann, K.G. and Braun, H., Exp. Cell Res., 2009, 315, 50-66
The Na(+)/H (+) exchanger modulates long-term potentiation in rat hippocampal slices.
Rönicke, R., Schröder, U.H., Böhm, K. and Reymann, K.G., Naynyn-Schmiedebergs Archiv, 2009, 379, 233-239
Aβ mediated diminution of MTT reduction-an artefact of single cell culture?
Rönicke, R., Klemm, A., Meinhardt, J., Schröder, U.H., Fändrich, M. and Reymann, K.G., PLOS PLoS ONE. 2008, 3, e3236
The potent non-competitive mGlu1 receptor antagonist (3aS,6aS)-6a-naphthalen-2-ylmethyl-5-methyliden-hexahydro-cyclopental[c]furan-1-on differentially affects synaptic plasticity in area cornu ammonis 1 of rat hippocampal slices and impairs acquisition in the water maze task in mice.
Schröder, U.H., Müller, T., Schreiber, R., Stolle, A., Zuschratter, W., Balschun, D., Jork, R. and Reymann, K.G., Neuroscience, 2008, 19, 385-395
Anti-inflammatory treatment with the p38 inhibitor SB239063 is neuroprotective, decreases the number of activated microglia and facilitates neurogenesis in oxygen-glucose-deprived hippocampal slice cultures.
Strassburger, M., Braun, H. and Reymann, K.G., Eur. J. Pharmacol. , 2008, 592, 55-61
Microglia cells protect neurons by direct engulfment of invading neutrophil granulocytes: a new mechanism of CNS immune privilege.
Neumann, J., Sauerzweig, S., Rönicke, R., Gunzer, F., Dinkel, K., Ullrich, O., Gunzer, M. and Reymann, K.G., J. Neurosci., 2008, 28, 5965-5975
Pattern of time-dependent reduction of histologically determined infarct volume after focal ischaemia in mice.
Henrich-Noack, P., Baldauf, K., Reiser, G. and Reymann, K.G., Neurosci. Lett. , 2008, 432, 141-145
P2 receptor antagonist TNP-ATP protects hippocampus from oxygen and glucose deprivation cell death.
Cavaliere, F., Amadio, S., Dinkel, K., Reymann, K., VolonteC., J. Pharmacol. Exp. Ther., 2007, 323, 70-77
Predictive value of changes in electroencephalogram and excitatory postsynaptic field potential for CA1 damage after global ischaemia.
Henrich-Noack, P. Alexandre G. Gorkin, Klaus G. Reymann, Exp. Brain Res. 2007, 181, 79-86.
A novel immune-based therapy for stroke induces neuroprotection and supports neurogenesis.
Ziv, Y., Finkelstein, A., Geffen, Y., Kipnis, J., Smirnov, I., Shpilman, S., Vertkin, I., Kimron, M., Lange, A., Hecht, T., Reyman, K.G., Marder, J.B., Schwartz, M., and Yoles, E., Stroke, 2007, 38, 774-782
The late maintenance of hippocampal LTP: requirements, phases, 'synaptic tagging' 'late associativity' and implications.
Reymann, K.G., and Frey, J.U., Neuropharmacol., 2007, 52-24-40
Embryonic stem cell-derived neural precursors survive after transplantation into the ischemic cortex and differentiate into functional neurons.
Bühnemann, C., Scholz, A., Bernreuther, C., Malik, C.Y., Braun, H., Schachner, M., Reymann, K.G., (equally contributed with MD), and Dihné, M., Brain, 2006, 129, 3238-48
Cultivation of primary cortical neurons from embryonic rats under serum free conditions using Matrigel and StartV-medium.
Braun, H., Bühnemann, C., and Reymann, K.G., J. Neurosci. Meth., 2006, 157, 32-38
Neural regeneration peptides: A new class of chemoattractive and neuronal survival promoting small, secreted proteins.
Gorba, T., Bradoo, P., Antonic, A., Marvin, K., Xu, D., Lobie, P., Reymann, K.G., Gluckman, P.D., and Sieg, F., Exp. Cell Res., 2006, 312, 3060-3074
The subventricular zone releases factors which can be protective in oxygen/glucose deprivation-induced cortical damage: an organotypic study.
Cavaliere, F., Dinkel, K., and Reymann, K.G., Exp. Neurol., 2006, 201, 66-74
Neurogenesis in organotypic hippocampal slice cultures inhibited by neuronal damage and inflammation early after oxygen-glucose deprivation restores at later time point.
Chechneva, O., Dinkel, K., Cavaliere, F., Martinez-Sanchez, M., and Reymann, K.G., Neurobiol. Disease, 2006, 23, 247-259
Microglia provide neuroprotection after ischemia.
Neumann, J., Gunzer, M., Gutzeit, H.O., Ullrich, O., Reymann, K.G., and Dinkel, K., FASEB J., 2006, 20, 714-716
Focal ischemia induces expression of protease-activated receptor1 (PAR1) and PAR3 on microglia and enhances PAR4 labeling in the penumbra.
Henrich-Noack, P., Riek-Burchardt, M., Baldauf, K., Reiser, G., and Reymann, K.G., Brain Res., 2006, 1070, 232-241
Preconditioning with thrombin can be protective or worsen damage after endothelin-1-induced focal ischemia in rats.
Henrich-Noack, P., Striggow, F., Reiser, G., and Reymann, K.G., J. Neurosci. Res., 2006, 83, 469-475
Increase in proliferation and gliogenesis but decrease of early neurogenesis in the rat forebrain shortly after transient global ischemia.
Pforte, C., Henrich-Noack, P., Baldauf, K., and Reymann, K.G., Neurosci., 2005, 136, 1133-1146
Microglia response and P2 receptor participation in oxygen/glucose deprivation-induced cortical damage.
Cavaliere, F., Dinkel, K., and Reymann, K.G., Neurosci., 2005, 136, 615-623
Precursor cells from lateral ventricle are present in juvenile organotypic hippocampal slice cultures and display differ from dentate gyrus precursors neurogenic properties.
Chechneva, O., Dinkel, K., Schrader, D., and Reymann, K.G., Neurosci., 2005, 136, 343-355
Influence of EGF/bFGF treatment on proliferation, neurogenesis and infarct volume after transient focal ischemia.
Baldauf, K., and Reymann, K.G., Brain Res., 2005, 1056, 158-167
Neurogranin/RC3 enhances long-term potentiation and learning by promoting calcium-mediated signaling.
Huang, K.-P., Huang, F.L., Jäger, T., Li, L., Reymann, K.G., and Balschun, D., J. Neurosci., 2004, 24, 10660-10669
The ATP-regulated K+ -channel inhibitor HMR-1372 affects synaptic plasticity in hippocampal slices.
Schröder, U.H., Hock, F.J., Wirth, K., Englert, H.C., and Reymann, K.G., Eur. J. Pharmacol., 2004, 502, 99-104
Na+ and Ca2+ homeostasis pathways, cell death and protection after oxygen-glucose-deprivation in organotypic hippocampal slice cultures.
Martínez-Sánchez, M., Striggow, F., Schröder, U., Kahlert, S., Reymann, K.G., and Reiser, G., Neuroscience, 2004 , 128, 729-740
Detection of chronic sensorimotor impairments in the ladder rung walking task in rats with endothelin-1-induced mild focal ischemia.
Riek-Burchardt, M., Henrich-Noack, P., Metz, G.A., and Reymann, K.G., J. Neurosci. Meth., 2004, 137, 227-233
Transient focal ischemia in rat brain differentially regulates mRNA expression of protease-activated receptors 1 to 4.
Rohatgi, T., Henrich-Noack, P., Sedehizade, F., Goertler, M., Wallesch, C.W., Reymann, K.G., and Reiser G., Neurosci. Res., 2004, 75, 273-279
Proliferating cells differentiate into neurons in the hippocampal CA1 region of gerbils after global cerebral ischemia.
Schmidt, W., and Reymann, K.G., Neurosci. Lett., 2002, 334, 153-156
Neurogranin is involved in the modulation of calcium/calmodulin-dependent protein kinase II, synaptic plasticity, and spatial learning: studies with knockout mice.
Pak, J.H., Freesia L. Huang, F.L., Li J., Balschun, D., Reymann, K.G., Chiang, C., Westphal, H., and Huang, K.-P., Proc. Natl. Acd. Sci., 2001, 97, 11232-11237
Inhibition of different pathways influncing Na+ homeostasis protects organotypic hippocampal slice cultures from hypoxia/hypoglycemia.
Breder J., Sabelhaus, C.F., Opitz, T., Reymann, K.G., and Schröder, U.H., Neuropharmacol., 2000, 39 1779-1787
The protease thrombin is an endogenous mediator of hippocampal neuroprotection against ischemia at low concentrations but causes degeneration at high concentrations.
Striggow, F., Riek, M., Breder, J., Henrich-Noack, P., Reymann, K.G., and Reiser, G., Proc. Natl. Acd. Sci., 2000, 97, 2264-2269
Distinct influence of the group III metabotropuc glutamate receptor agonist (R,S)-PPG on differnt forms of neurodegeneration.
Henrich-Noack, P., Flor, P.J., Sabelhaus, C., Prass, K., Dirnagl, U., Gasparini, A., Sauter, M., Rudin, M., and Reymann, K.G., Neuropharmacol., 2000, 39, 911-917
A specific role for mGluRs in hippocampal LTP and hippocampus-dependent spatial learning.
Balschun, D., Manahan-Vaughan, D., Wagner, T., Behnisch, T., Reymann, K.G, and Wetzel, W., Learning and Memory, 1999, 6, 138-152
Long-term potentiation in rat CA1 neurons requires post-synaptic calcium induced calcium release.
Szinyei, C., Behnisch, T., Reiser, G., and Reymann, K.G., J. Physiology, 1999, 516, 855-868
Protective effect of class I metabotropic glutamate receptor activation against hypoxic/hypoglycemic injury in rat hippocampal slices: timing and involvement of PKC.
Schröder, U., Opitz, T., Jäger, T., Sabelhaus, C.F., Breder, J., and Reymann, K.G., Neuropharmacol., 1999, 38, 209-216