By means of electrophysiological methodology, research of this group is focused on the cellular and molecular mechanisms of anesthetics and other central effective compounds.


German Version

In the last ten years the spectrum of methods has been complemented by imaging techniques such as Ca2+-Imaging and Voltage-sensitive dye Imaging (VSDI).



Present Co-workers:

Prof. Dr. Gerhard Rammes (Groupleader)
Dr. Martina Bürge
Carolin Knoll
Shi Dai
Xing Xing Wang
Nina Bayer
Xenia Puig
Nour Kassab El Dine
Arpit Pradhan Kumar
Andreas Blaschke

Contact:

Prof. PhD Dr. Gerhard Rammes
  g.rammes@tum.de(link sends e-mail)
Telefonnummer 089 4140-9839

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 and Intensive Care 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 GABAA 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

Collaborators

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


Key Publications

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

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.

Rammes, G., Seeser, F., Mattusch, K., Zhu, K., Haas, L., Kummer, M., Heneka, M., Herms, J., Parsons, C. G., 2018. The NMDA receptor antagonist Radiprodil reverses the synaptotoxic effects of different amyloid-beta (Abeta) species on long-term potentiation (LTP). Neuropharmacology 140, 184-192.

Burge, M., Kratzer, S., Mattusch, C., Hofmann, C., Kreuzer, M., Parsons, C. G., Rammes, G., 2019. The anaesthetic xenon partially restores an amyloid beta-induced impairment in murine hippocampal synaptic plasticity. Neuropharmacology 151, 21-32.

Diggelen, F. v., Hrle, D., Apetri, M., Christiansen, G., Rammes, G., Tepper, A., Otzen, D. E., 2019. Two conformationally distinct α-synuclein oligomers share common epitopes and the ability to impair long-term potentiation. PLoS ONE.

Pigoni, M., Hsia, H. E., Hartmann, J., Rudan Njavro, J., Shmueli, M. D., Muller, S. A., Guner, G., Tushaus, J., Kuhn, P. H., Kumar, R., Gao, P., Tran, M. L., Ramazanov, B., Blank, B., Hipgrave Ederveen, A. L., Von Blume, J., Mulle, C., Gunnersen, J. M., Wuhrer, M., Rammes, G., Busche, M. A., Koeglsperger, T., Lichtenthaler, S. F., 2020. Seizure protein 6 controls glycosylation and trafficking of kainate receptor subunits GluK2 and GluK3. Embo J 39, e103457.

German Version