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Experimental Neuropharmacology

[German Version]


By means of electrophysiological methodology, research of the Department for Anaesthesiology has been focused on the cellular and molecular mechanisms of anesthetics and other central effective compounds. In the last ten years the spectrum of methods has been complemented by imaging techniques such as Calcium-Imaging and Voltage-sensitive dye Imaging (VSDI).

Present Co-workers:

Prof. Dr. Gerhard Rammes (Groupleader)
Dr. Martina Bürge
Carolin Knoll
Shi Dai
Tatjana Neumüller
Xing Xing Wang
Taylan Yazgan
Nina Bayer
Andreas Blaschke

Funding

Beside institutes own funds, also funding of the German Research Funding Organisation (DFG), internal faculty commission for clinical research (KKF) and industrial money is available.

Spatial and instrumental equipment

The laboatories of the Department of Anaesthesiology are located at the area of the Klinik rechts der Isar. Experiments will be conducted with extra- and intracellular recording techniques, as well as imaging techniques.

Areas of investigation

  • Physiology and pathophysiology of synaptic transmission in the CNS.
  • Synaptic plasticity in the hippocampus and amygdala and its modulation (LTP, long-term potentiation, LTD, long-term depression).
  • Performing pharmacological and physiological research in the fields of anaesthesia, depression and neurodegeneration (focus on Alzheimer’s disease (AD))
  • Aβ species: neurotoxic effects and the prevention by receptor modulators, aggregation inhibitors, interaction with autophagy-related signalling cascades

Research focus

  • Interaction of anaesthetics (isoflurane, sevoflurane, ketamine, xenon), benzodiazepines and neurosteroids with the Aß-mediated pathophysiology of AD. The question is, how such drugs modulate the synaptotoxic effects of Aß.
  • We are also interested in the involvement of microglia and astrocytes in synaptic pruning, mechanisms important for dynamic properties of spines (persistent, gained and lost spine rate) which are critical for the function of neural circuits and synaptic plasticity. Crucial for these processes are proteins like Nectin, Megf10, MERKT and Cx3CR1. Since cognitive performance is highly dependent on quantity and functionality of dendritic spines, we are highly interested in if and how anesthetics and Aß affects those mechanisms.
  • Modulation of GABA(A) receptor subtypes by neurosteroids and anesthetics: Identification of molecular targets for neuroprotection

Experimental methods

  • extra- und intracellular electrophysiological recordings
  • Combined application of laser stimulation (uncaging of neurotransmitter by UV-light)
  • on dendrites of pyramidal neurons (patch-clamp in whole-cell mode) and
  • infrared-guided microscopy
  • In vitro recording of cultured neurons with stable or transient transfected ion channels
  • Behavioural tests (in collaboration): Fear conditioning, Modified Hole-Board Test
  • Methods in molecular biology: receptor transfection, in situ hybridisation and immunohistochemistry, Cell culture, Western blotting, Immunoprecipitation
  • Ca2+-Imaging in neurons, astrocytes and slices
  • Voltage-Sensitive-Dye-Imaging (VSDI) in slices

Kollaborators

  • Prof Dr. Rainer Rupprecht, Bezirksklinikum Regensburg, Universitätsstraße 84, 93053 Regensburg
  • Dr. Theo Rein, Max-Planck-Institut of Psychiatry, Kraepelinstr. 10, 80804 München
  • Dr. Chris G. Parsons, Head: In Vitro Pharmacology, Preclinical Research & Development, Merz Pharmaceuticals GmbH, Eckenheimer Landstraße 100, 60318 Frankfurt am Main 1
  • Prof Dr. Jochen Herms, German Center for neurodegenerative diseases (DZNE), Feodor-Lynen Str. 17, 81377 München
  • Prof Dr. Bernd Antkowiak, University of Tübingen, Waldhörnlestraße 22, 72072 Tübingen
  • Prof Dr. Aphrodite Kapurniotu, Technische Universität München, Emil-Erlenmeyer-Forum 5, 85354 Freising-Weihenstephan
  • Research groups Department of Anaesthesiology

Key Publications

Andreetto, E., Malideli, E., Yan, L. M., Kracklauer, M., Farbiarz, K., Tatarek-Nossol, M., Rammes, G., Prade, E., Neumuller, T., Caporale, A., Spanopoulou, A., Bakou, M., Reif, B., Kapurniotu, A., 2015. A Hot-Segment-Based Approach for the Design of Cross-Amyloid Interaction Surface Mimics as Inhibitors of Amyloid Self-Assembly. Angew Chem Int Ed Engl 54, 13095-13100.

Haseneder, R., Kratzer, S., Kochs, E., Eckle, V. S., Zieglgansberger, W., Rammes, G., 2008. Xenon reduces N-methyl-D-aspartate and alpha-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor-mediated synaptic transmission in the amygdala. Anesthesiology 109, 998-1006.

Haseneder, R., Starker, L., Berkmann, J., Kellermann, K., Jungwirth, B., Blobner, M., Eder, M., Kochs, E., Rammes, G., 2013. Sevoflurane anesthesia improves cognitive performance in mice, but does not influence in vitro long-term potentation in hippocampus CA1 stratum radiatum. PLoS ONE 8, e64732.

Kratzer, S., Mattusch, C., Kochs, E., Eder, M., Haseneder, R., Rammes, G., 2012. Xenon Attenuates Hippocampal Long-term Potentiation by Diminishing Synaptic and Extrasynaptic N-methyl-D-aspartate Receptor Currents. Anesthesiology 116, 673-682.

Martinez-Coria, H., Green, K. N., Billings, L. M., Kitazawa, M., Albrecht, M., Rammes, G., Parsons, C. G., Gupta, S., Banerjee, P., LaFerla, F. M., 2010. Memantine improves cognition and reduces Alzheimer's-like neuropathology in transgenic mice. Am J Pathol 176, 870-880.

Mattusch, C., Kratzer, S., Buerge, M., Kreuzer, M., Engel, T., Kopp, C., Biel, M., Hammelmann, V., Ying, S. W., Goldstein, P. A., Kochs, E., Haseneder, R., Rammes, G., 2015. Impact of Hyperpolarization-activated, Cyclic Nucleotide-gated Cation Channel Type 2 for the Xenon-mediated Anesthetic Effect: Evidence from In Vitro and In Vivo Experiments. Anesthesiology 122, 1047-1059.

Nothdurfter, C., Rupprecht, R., Rammes, G., 2012. Recent developments in potential anxiolytic agents targeting GABAA/BzR complex or the translocator protein (18kDa) (TSPO). Curr Top Med Chem 12, 360-370.

Parsons, C. G., Ruitenberg, M., Freitag, C. E., Sroka-Saidi, K., Russ, H., Rammes, G., 2015. MRZ-99030 - A novel modulator of Abeta aggregation: I - Mechanism of action (MoA) underlying the potential neuroprotective treatment of Alzheimer's disease, glaucoma and age-related macular degeneration (AMD). Neuropharmacology 92, 158-169.

Rammes, G., Gravius, A., Ruitenberg, M., Wegener, N., Chambon, C., Sroka-Saidi, K., Jeggo, R., Staniaszek, L., Spanswick, D., O'Hare, E., Palmer, P., Kim, E. M., Bywalez, W., Egger, V., Parsons, C. G., 2015. MRZ-99030 - A novel modulator of Abeta aggregation: II - Reversal of Abeta oligomer-induced deficits in long-term potentiation (LTP) and cognitive performance in rats and mice. Neuropharmacology 92, 170-182.

Rammes, G., Hasenjager, A., Sroka-Saidi, K., Deussing, J. M., Parsons, C. G., 2011. Therapeutic significance of NR2B-containing NMDA receptors and mGluR5 metabotropic glutamate receptors in mediating the synaptotoxic effects of beta-amyloid oligomers on long-term potentiation (LTP) in murine hippocampal slices. Neuropharmacology 60, 982-990.

Rammes, G., Mattusch, C., Wulff, M., Seeser, F., Kreuzer, M., Zhu, K., Deussing, J. M., Herms, J., Parsons, C. G., 2017. Involvement of GluN2B subunit containing N-methyl-d-aspartate (NMDA) receptors in mediating the acute and chronic synaptotoxic effects of oligomeric amyloid-beta (Abeta) in murine models of Alzheimer's disease (AD). Neuropharmacology 123, 100-115.

Rupprecht, R., Rammes, G., Eser, D., Baghai, T. C., Schule, C., Nothdurfter, C., Troxler, T., Gentsch, C., Kalkman, H. O., Chaperon, F., Uzunov, V., McAllister, K. H., Bertaina-Anglade, V., La Rochelle, C. D., Tuerck, D., Floesser, A., Kiese, B., Schumacher, M., Landgraf, R., Holsboer, F., Kucher, K., 2009. Translocator protein (18 kD) as target for anxiolytics without benzodiazepine-like side effects. Science 325, 490-493.

Zhu, K., Xiang, X., Filser, S., Marinkovic, P., Dorostkar, M. M., Crux, S., Neumann, U., Shimshek, D. R., Rammes, G., Haass, C., Lichtenthaler, S. F., Gunnersen, J. M., Herms, J., 2016. Beta-Site Amyloid Precursor Protein Cleaving Enzyme 1 Inhibition Impairs Synaptic Plasticity via Seizure Protein 6. Biol Psychiatry.

Contact:
Prof. Dr. Gerhard Rammes, g.rammes(at)tum.de, Phone 089-4140-9839

[German Version]