Klinik für Psychische Gesundheit

Institute of Translational Neuroscience

Scientific Mission

The Institute of Translational Neuroscience is an independent research institution at the Medical Faculty of the Westfälische Wilhelms-University Münster embedded in the Department of Mental Health at the Münster University Medical Center (UKM, Director: Prof. Dr. med. Bernhard Baune). It is dedicated to provide new options for diagnostic and/or therapeutic strategies for human diseases of the nervous system. This “bench to bedside” approach builds on molecular research pursued during the last 30 years which paved the avenue for novel therapeutic strategies to be assessed in man. It follows the idea that neuroscience is a discipline providing understanding of human disease and eventually its cure, rather than to explain man itself. Translation defines the goal of basic research, the patient. While experimental studies are pursued in close collaboration with the Institute of Anatomy, University of Cologne (Director: Prof. Dr. med. Johannes Vogt), clinical studies are performed in close collaboration with the Institute of Translational Psychiatry, WWU Münster (Director: Prof. Dr. med. Dr. phil. Udo Dannlowski).

In addition to translational research, philosophical aspects of the mind-body debate are addressed and a focus of the Institute’s teaching activities. The ever-recurring attempts of the neurosciences to explain all mental phenomena in physical terms alone are revised by critical reappraisal of classical concepts, e.g. Wilder Penfield’s “storehouse of memories”. Our analyzes question the idea of a realization of memory in solely naturalistic terms. These studies are performed in part at the Montreal Neurological Institute (Prof. Dr. Richard Leblanc, Prof. Dr. Jack Antel), Quebec, Canada, and in close collaboration with Prof. Dr. med. Frank Stahnisch at the Hotchkiss Brain Institute, University of Calgary, Alberta, Canada.

Translational research:

Our previous work using molecular and genetic approaches in model systems, but also human cohort data performed at the Institutes of Cell- and Neurobiology at the Charité-University Medical Center Berlin (from 1994-2009) and Microscopic Anatomy and Neurobiology at the University Medical Center of the Johannes Gutenberg-University Mainz (from 2010-2016) resulted in the discovery of a novel molecular pathway at the excitatory synapse in the brain. A role for bioactive lipid signaling at the synapse was first demonstrated by the detection of a new subgroup of lipid-phosphate phosphatases (LPPs)-like molecules, which we named plasticity related gene 1 (PRG-1, Bräuer et al., Nature Neuroscience, 2003). Unlike the classical LPPs, however, PRG-1 exhibits no phosphatase activity, but is a pore for lipid phosphatidic acid (LPA), a bioactive lipid acting on specific LPA1-6-receptors, thereby modulating excitatory transmission (Trimbuch et al., Cell 2009). This bioactive lipid signaling further involves the LPA-synthesizing molecule autotaxin (ATX) which is located in perisynaptic lamellae of astrocytes and converts lipid phosphatidic choline (LPC) to LPA in the synaptic cleft (Thalman et al., Molecular Psychiatry 2018). Dietary and pharmacological Intervention into this signaling pathway appears to be a novel therapeutic strategy to eventually treat psychiatric disease (Vogt et al., EMBO Mol Med 2015) and eating disorders. Building on these fundamental insights into the direct impact of peripheral metabolism on cortical function, clinical studies are on their way to develop these new therapeutic options to the patient’s benefit.

Philosophical studies:

Research on memory has been a major focus in the neurosciences over the past decades. An important advancement of memory research was achieved by Wilder Penfield at the Montreal Neurological Institute, who reported from the 1930s to the 1950s on experiential phenomena induced by electrical brain stimulation in humans, implying neuronal causation of memory. These reports as well as those on patient H. M. by Brenda Milner at the same institution continue to be referenced as ground-breaking, and neuroscientists have addressed the topic of memory from a range of sub-disciplines. Continuing experimental work by Nobel laureates Eric Kandel, John O’Keefe, as well as Edvard and May-Britt Moser related Penfield’s patient documentation to experiential phenomena. Assessing original charts of Penfield’s patients, however, questioned the stances that the neurosciences can uncover the “storehouse of memories”. Human memory must rather be regarded as context-sensitive and as an active reconstructive process, than a simple recording of events. Hence, strategies aiming at naturalizing all phenomena of mind (including memory) to cellular and molecular mechanisms cannot convincingly refer to Penfield’s electrophysiological studies, and remain unbacked but far-fetching claims to “understand man himself”. Further analyzes of such claims in the neuroscience literature are on their way.

Team

The following members of the Institute of Translational Psychiatry, WWU Münster (Director: Prof. Dr. med. Dr. phil. Udo Dannlowski) are collaborating members of the Institute of Translational Neuroscience:

Projects

  • Lipid Signaling at the glutamatergic synapse: Mechanisms and impact.

  • ATX-inhibiting drugs as a new therapeutic option for the treatment of psychiatric and eating disorders.

  • Assessing the claims of the neurosciences to naturalize mind.

Current funding

  • ERC Proof-of-Concept Grant PsychAID

Selected publications

Translational research:

Thalman C*, Horta G*, Qiao L, Endle H, Tegeder I, Cheng H, Laube G, Sigurdsson T, Hauser MJ, Tenzer S, Distler U, Aoki J, Morris AJ, Geisslinger G, Röper J, Kirischuk S, Luhmann HJ, Radyushkin K, Nitsch R*, Vogt J* (2018) Synaptic phospholipids as a new target for cortical hyperexcitability and E/I balance in psychiatric disorders. Mol Psychiatry. 23(8):1699-1710. *equal contribution

Cheng J*, Sahani S*, Hausrat TJ*, Yang JW, Ji H, Schmarowski N, Endle H, Liu X, Li Y, Böttche R, Radyushkin K, Maric HM, Hoerder-Suabedissen A, Molnár Z, Prouvot PH, Trimbuch T, Ninnemann O, Huai J, Fan W, Visentin B, Sabbadini R, Strømgaard K, Stroh A, Luhmann HJ, Kneussel M, Nitsch R* Vogt J* (2016) Precise Somatotopic Thalamocortical Axon Guidance Depends on LPA-Mediated PRG-2/Radixin Signaling. Neuron. 5;92(1):126-142: *equal contribution

Vogt J*, Yang J*, Mobascher A*, Cheng J, Li J, Liu X, Baumgart J, Thalman C, Kirischuk S, Unichenko P, Horta G, Radyushkin K, Stroh A, Richers S, Sahragard N, Distler U, Tenzer S, Qiao L, Lieb K, Tüscher O, Binder H, Ferreiros N, Tegeder I, Morris A, Groppa S, Winterer G*, Luhmann H*, Huai J*, Nitsch R* (2016) Molecular cause and functional impact of altered synaptic lipid signaling due to a prg-1 gene SNP. EMBO Mol Med. 8: 25–38. *equal contribution; see also News & Views: Stutz B and Horvath TL (2016) Synaptic lipids in cortical function and psychiatric disorders EMBO Mol Med. 8: 3-5.

Trimbuch T*, Beed P*, Vogt J*, Schuchmann S, Maier N, Kintscher M, Breustedt J, Schuelke M, Streu N, Kieselmann O, Brunk I, Laube G, Strauss U, Battefeld A, Wende H, Birchmeier C, Wiese S, Sendtner M, Kawabe H, Kishimoto-Suga M, Brose N, Baumgart J, Geist B, Aoki J, Savaskan NE, Bräuer AU, Chun J, Ninnemann O, Schmitz D*, Nitsch R* (2009) Synaptic PRG-1 modulates excitatory transmission via lipid phosphate-mediated signaling. Cell 138:1222-35. *equal contribution

Eljaschewitsch E, Witting A, Mawrin C, Lee T, Schmidt PM, Wolf S, Hörtnagl H, Raine CS, Schneider-Stock R, Nitsch R*, Ullrich O* (2006) The endocannabinoid anandamide protects neurons during CNS inflammation by induction of MKP-1 in Microglial Cells. Neuron 49: 67-79. *equal contribution

Aktas O, Smorodchenko A, Brocke S, Infante-Duarte C, Topphoff US, Vogt J, Prozorovski T, Meier S, Osmanova V, Pohl E, Bechmann I, Nitsch R*, Zipp F* (2005) Neuronal damage in autoimmune neuroinflammation mediated by the death ligand TRAIL. Neuron 46:421-432.    *equal contribution

Bräuer AU, Savaskan NE, Kühn H, Prehn S, Ninnemann O, Nitsch R (2003) A new phospholipid phosphatase, PRG-1, is involved in axon growth and regenerative sprouting. Nat Neurosci 6:572-78.

Ullrich O, Diestel A, Eyüpoglu I, Nitsch R (2001) Regulation of microglial expression of integrins by poly(ADP-ribose) polymerase-1. Nat Cell Biol 3:1035-42.

Nitsch R, Bechmann I, Deisz RA, Haas D, Lehmann TN, Wendling U, Zipp F (2000) Human brain-cell death induced by tumour-necrosis-factor-related apoptosis-inducing ligand (TRAIL). Lancet 356:827-828.

Nitsch R and Frotscher M (1992) Reduction of posttraumatic transneuronal "early gene" activation and dendritic atrophy by the NMDA-receptor antagonist MK-801. Proc Natl Acad Sci USA 89: 5197-5200.

 

Philosophical studies:

Nitsch R, Stahnisch FW. (2018) Neuronal Mechanisms Recording the Stream of Consciousness-A Reappraisal of Wilder Penfield's (1891-1976) Concept of Experiential Phenomena Elicited by Electrical Stimulation of the Human Cortex. Cerebral Cortex 28(9):3347-3355.

Nitsch R (2012) Gehirn, Geist und Bedeutung. Zur Stellung der Hirnforschung in der Leib-Seele-Diskussion. Mentis.

Stahnisch FW, Nitsch R. (2002) Santiago Ramón y Cajal's concept of neuronal plasticity: the ambiguity lives on. Trends Neurosci. 25(11):589-91.

 
 
 
 

Director: Prof. Dr. med. Dr. phil. Robert Nitsch

Tel.: +49 (0) 251 83-56678

E-Mail: nitschr(at)­uni-muenster(dot)­de

CV

Administration assistance: Karin Biesenroth

Tel.: +49 (0)251 / 83-56618

Fax: +49 (0)251 / 83-56988

E-Mail: office.itn(at)­uni-muenster(dot)­de // lehre.itn(at)­uni-muenster(dot)­de (teaching)