Stress research - interindividual differences in resistance (resilience) to stressful events

In recent years there has been increasing evidence of a possible pathogenetic connection between chronic stress and the development of affective disorders. In many patients - based on an individual genetic predisposition - stress seems to trigger the development of disease episodes. However, the following questions are still largely unanswered:

Which molecular mechanisms mediate the long-term negative consequences of long-term stress on neuronal function and ultimately the regulation of emotions? And by which protective mechanisms are those individuals protected from the development of stress-related mental illness in whom mental health is maintained despite exposure to significant stressors?

Such protective neurobiological mechanisms are potential resilience mechanisms that we are currently interested in exploring. With the identification of a novel actin-interacting protein (DRR1), we have been able to characterize a molecular factor which, through its stress and glucocorticoid regulation, is a direct link between exposure to stressful events and persistent changes in neuronal structure and function up to complex behavior (cognitive performance).

Key publications 

• van der Kooij MA, Masana M, Rust MB, Müller MB (2016). The stressed cytoskeleton: how actin dynamics can shape stress-related consequences on synaptic plasticity and complex behavior. Neurosci Biobehav Rev 62, 69–75
• Kalisch R, Müller MB, Tüscher O (2014). A conceptual framework for the neurobiological study of resilience. Behav Brain Sci. Aug 27:1-49.
• Masana M, Su Y-A, Jansen L, Westerholz S, Liebl C, Wagner KV, Schmidt MV, Rein T, Müller MB (2014). The stress-inducible actin-interacting protein DRR1 shapes social behavior. Psychoneuroendocrinology 48:98-110
• Wang XD, Su Y, Wagner KV, Avrabos C, Scharf SH, Hartmann J, Wolf M, Liebl C, Kühne C, Wurst W, Holsboer F, Eder M, Deussing JM, Müller MB, Schmidt MV (2013). Nectin-3 Links CRHR1 Signaling to Stress-Induced Memory Deficits and Spine Loss. Nature Neuroscience 16(6):706-13
• Schmidt MV, Schülke J-P, Liebl C, Stiess M, Avrabos C, Bock J, Wochnik GM, Davies HA, Zimmermann N, Scharf SH, Trümbach D, Wurst W, Zieglgänsberger W, Turck C, Holsboer F, Stewart MG, Bradke F, Eder M, Müller MB*, Rein T* (2011). The tumor suppressor DRR1 is a stress-induced actin bundling factor that modulates synaptic efficacy and cognition. Proceedings of the National Academy of Science 108: 17213-17218 - *geteilte Letztautorenschaft; diese Arbeit wurde auch in den Research Highlights in Nature diskutiert (Stress alters brain connections. Nature 2011; 478: 159)
• Schmidt MV, Trümbach D, Weber P, Wagner K, Scharf SH, Liebl C, Datson N, Namendorf C, Gerlach T, Kühne C, Uhr M, Deussing JM, Wurst W, Binder EB, Holsboer F, Müller MB (2010). Individual stress vulnerability is predicted by short-term memory and AMPA receptor subunit ratio in the hippocampus. The Journal of Neuroscience 30:16949-16958
• Müller MB, Zimmermann S, Sillaber I, Hagemeyer TP, Timpl P, Kormann MSD, Droste S, Deussing JM, Kühn R, Reul JMHM, Holsboer F, Wurst W (2003). Limbic corticotropin-releasing hormone receptor 1 mediates anxiety-related behavior and hormonal adaptation to stress. Nature Neuroscience 6: 1100-1107