The Quarterly Publication Award (QPA) III/2024 from the Anatomische Gesellschaft has been awarded to Dr. Oliver Tüscher, Prof. Dr. Johannes Vogt and coworkers involved in this study for their publication on the regulation of mental disorders with enzyme inhibitors published in Molecular Psychiatry.
The study describes a connection between synaptic lipid signals in the brain and mental illness: Teams led by Professor Dr. med. Johannes Vogt at the Department of Molecular and Translational Neurosciences at the University of Cologne and Professor Dr. med. Robert Nitsch (equally contributing last author of the study) at the Institute of Translational Neuroscience at the University of Münster investigated the role of the enzyme autotaxin and its counterpart, the protein PRG-1, in regulating the balance between excitation and inhibition in the brains of humans and mice. They were able to prove that a genetic disorder identified in humans leads to an increase in bioactive endogenous fats in the brain, which results in an imbalance between excitation and inhibition in brain circuits and favors, for example, depression, anxiety and increased susceptibility to stress. However, treatment with an enzyme inhibitor that prevents the activation of fats can restore the balance and alleviate the symptoms. The studies were carried out as part of the Collaborative Research Center 1451 “Key mechanisms of normal and disease-related impaired motor control” (spokesperson: Professor Dr. Gereon R. Fink, University of Cologne).
Prof. Vogt explains: “The publication is a milestone for us, as for the first time it has been shown in parallel in humans and in the mouse model that the data collected in mice can be collected in a comparable way in humans. This fact enables us to use mouse lines with genetic alterations in synaptic lipid signaling as a model for psychiatric diseases and to test therapeutic options in the mouse in a translational setting. Accordingly, the data collection was very complex.”
The research project led by Johannes Vogt and Robert Nitsch as part of the CRC is concerned with the balance between excitation and inhibition in the brain and its effect on motor function. This balance also plays an important role in mental disorders. During excitation, neuronal circuits cause information to be passed on and activate further neurons; during inhibition, this passing on of information is interrupted.
Tüscher O, Muthuraman M, Horstmann JP, Horta G, Radyushkin K, Baumgart J, Sigurdsson T, Endle H, Ji H, Kuhnhäuser P, Götz J, Kepser LJ, Lotze M, Grabe HJ, Völzke H, Leehr EJ, Meinert S, Opel N, Richers S, Stroh A, Daun S, Tittgemeyer M, Uphaus T, Steffen F, Zipp F, Groß J, Groppa S, Dannlowski U, Nitsch R, Vogt J. Altered cortical synaptic lipid signaling leads to intermediate phenotypes of mental disorders. Mol Psychiatry. 2024 Nov;29(11):3537-3552. doi: 10.1038/s41380-024-02598-2. Epub 2024 May 28. PMID: 38806692; PMCID: PMC11541086.
Contact:
Univ.-Prof. Dr. Johannes Vogt
Dept. of Molecular and Translational Neurosciences
Institute of Anatomy II
CECAD Cluster of Excellence for Aging Research
CMMC Center of Molecular Medicine Cologne
Universität zu Köln
Joseph-Stelzmann-Str. 60
50931 Cologne, Germany
Tel.: 0221-4785209
