Klinik für Psychische Gesundheit

Molecular Neuroscience & Experimental Psychiatry: From Gene over Brain Function to Mental Illness

Mental illnesses have a multifactorial etiology with a high heritability. Different polymorphisms of candidate genes are believed to susceptibility factors that increase the risk to develop a psychiatric disorder. Nowadays, it is general accepted that the individual risk for mental illness is composed of the interplay of genetic susceptibility and  environmental factors. Here, epigenetic mechanisms are believed to be the underlying mediators between genes and environment. Until now, the pathogenetic mechanisms of the psychiatric diseases such as autisms, anxiety disorders as well as schizophrenia are unknown. Identification of the underlying molecular mechanisms is thus crucial for understanding of pathogenesis and for developing novel therapeutic targets for these diseases.

Using a combined molecular biological, physiological and behavioral approach, we investigate the pathogenetic mechanisms of these diseases on molecular, cellular, network and behavior level in animal models:

a) investigating the functional role of different key molecules, such as neuregulin, ErbB4, RGS, neuroligin, neurexin, DHHC7 etc., in brain function and behavioral endophenotypes.

b) analyzing epigenetic processes and their functional consequences to uncover the underlying mechanisms which differentially regulate susceptibility genes using different mouse models.

c) studying genetic and environmental influences on behavioral endophenotypes using mutant mouse models

• Univ.-Prof. Dr. Weiqi Zhang
• Dr. rer. nat. Mingyue Zhang
• M.Sc. Biol. Nicole Kerkenberg
• CTA Christiane Schettler
• B. Sc. Helen Haupt
• B. Sc. Samuel Frommeyer
• B. Sc. Lucas Schwerdt
• Sadik-Emre Cicibas 
• Hannah Weiland

• The functional relevance of neuregulin1-ErbB4-mediated bidirectional signaling in brain structure, function and social behavior
• ZDHHC7-mediated palmitoylation of synaptic proteins as a key to understanding sex-specific differences in stress-related psychiatric disorders
• Epigenetic mechanisms as intergenerational mediators of stress resilience
• Circular RNAs as key modulator of neuronal plasticity in brain

• DFG_ZH 34/3-1: „The functional relevance of neuregulin1-III-mediated bidirectional signaling in prefrontal cortex of mouse“

1. Hohoff C, Zhang M, Ambrée O, Kravchenko M, Buschert J, Kerkenberg N, Gorinski N, Abdel Galil G, Schettler S, vom Werth K, Wewer M, Schneider I, Grotegerd D, Wachsmuth L, Faber C, Skryabin B, Brosius J, Ponimaskin E and Zhang W (2019): Deficiency of the palmitoyl acyltransferase ZDHHC7 impacts brain and behavior of mice in a sex-specific manner. Brain structure & function. 1–18.
2. Saffari R, Grotefeld K, Kravchenko M, Zhang M, Zhang W (2019): Calretinin⁺-neurons-mediated GABAergic inhibition in mouse prefrontal cortex. Prog Neuropsychopharmacol Biol Psychiatry. 94: 109658.
3. Dik A, Saffari R, Zhang M, Zhang W (2018): Contradictory effects of erythropoietin on inhibitory synaptic transmission in left and right prelimbic cortex of mice. Neurobiol Stress. 9: 113–123.
4. Wehr MC, Hinrichs W, Brzózka MM, Unterbarnscheidt T, Herholt A, Wintgens JP, Papiol S, Soto-Bernardini M, Kravchenko M, MZhang M, Nave K, Wichert S, Falkai P, Zhang W, Schwab M & Rossner M (2017): Spironolactone is an antagonist of NRG1-ERBB4 signaling and schizophrenia-relevant endophenotypes in mice. EMBO Mol Med. 9: 1448–1462.
5. Sakalem ME, Seidenbecher T, Zhang M, Saffari R, Kravchenko M, Wördemann S, Diederich K, Schwamborn JC, Zhang W, Ambrée O. (2017) Environmental enrichment and physical exercise revert behavioral and electrophysiological impairments caused by reduced adult neurogenesis. Hippocampus. 27(1):36-51.
6. Saffari R, Teng Z, Zhang M, Kravchenko M, Hohoff C, Ambrée O, Zhang W (2016): NPY(+)-, but not PV(+)-GABAergic neurons mediated long-range inhibition from infra- to prelimbic cortex. Transl Psychiatry. 6: e736.
7. Buschert J, Sakalem ME, Saffari R, Hohoff C, Rothermundt M, Arolt V, Zhang W, Ambrée O (2016) Prenatal immune activation in mice blocks the effects of environmental enrichment on exploratory behavior and microglia density. Prog Neuropsychopharmacol Biol Psychiatry 67:10–20.
8. Agarwal A, Zhang M, Trembak-Duff I, Unterbarnscheidt T, Radyushkin K, Dibaj P, de Souza D, Boretius S, Brzozka M, Steffens H, Berning S, Teng Z, Gummert M, Tantra M, Guest P, Willig K, Frahm J, Hell S, Bahn S, Rossner M, Nave K, Ehrenreich H, Zhang W and Schwab M (2014): Dysregulated Expression of Neuregulin-1 by Cortical Pyramidal Neurons Disrupts Synaptic Plasticity. Cell Rep. 8: 1130–1145.