Logo der Universitätsmedizin Mainz
Institute of Physiological Chemistry
 

Research Group “Molecular Mechanisms of Behavior” (Prof. Lutz)

We would like to understand how we learn and forget, how we are able to cope with stress (“stress resilience”) and why chronic stress can strongly affect our behavior (e.g. memory, social behavior, pain perception, eating behavior, energy metabolism). These behaviors are mainly controlled by the brain, but also by neuronal and hormonal interactions between the brain and peripheral organs. Behavioral patterns can also imprinted during development of the nervous system or by metabolic processes. Under pathophysiological conditions, changes in behavior and in cellular processes can be observed. Under certain circumstances, these changes can lead to psychiatric or neurological diseases. A detailed understanding of these neurobiological processes should aid to achieve better therapies or to prevent disease outbreak. We use a multidisciplinary approach to get new insights in these complex behavioral processes in the mouse animal model system. This includes genetic, pharmacological and biochemical methods as well as methods of cellular and molecular biology, histology and electrophysiology.

Effects of endocannabinoids
Fig. 1: Effects of endocannabinoids (left) and THC (right) on the cannabinoid CB1 receptor.

What are the functions of the endocannabinoid-system? How does THC act?

The discovery of endogenous binding proteins (the cannabinoid receptors) to Δ9-tetrahydrocannabinol (THC), isolated from Cannabis sativa, enabled the identification of endogenous cannabinoids (called endocannabinoids). Endocannabinoids are lipids, that mediate the communication between cells in the body and inside the cell. A central research topic deals with different physiological functions of this so-called endocannabinoid system. This recently described regulatory system seems to be important for the maintenance of the physical balance of the body (“homeostasis”). Furthermore, the system is critical to keep the organism resistant to stress and high demands (“stress resilience”).

We investigate this endogenous regulatory system

  • in the processing of fearful memories, anxiety and stress
  • in the regulation of eating behavior and energy metabolism
  • in relation to a protective mechanism against chronic stress
  • in the influence of chronic stress on pain perception
  • in the regulation of proliferation, migration and differentiation of neuronal precursor cells in the embryo and in the adult animal brain
  • in the signal transduction processes at the CB1 receptor, and
  • in the control of the excitability of neuronal networks.

Pharmacological interventions, which influence the activity of the endocannabinoid system, should evaluate a possible therapeutic use of cannabinoids in the behaviors mentioned above. In addition, we analyze how THC changes cellular processes during development and in the adult and thereby affects behavior.

Epigenetic changes and regulation of behavior

We study how the environment can influence behaviors. Regarding anxiety- or stress coping (“stress resilience”), memory formation or energy metabolism, genetic programs induce general behavioral reactions, which might be influenced by the individual life story. Here, covalent modifications of DNA (e.g. methylation) and chromatin (e.g. acetylation) play an important role. Therefore, we analyze epigenetic changes of genes which regulate behaviors, e.g. genes of the endocannabinoid system, and genes known to catalyze epigenetic processes.

Development of the nervous system, stem cells, stem cell therapy

Numerous signaling pathways are active in the embryo as well as in the adult, including the endocannabinoid system and neurotrophins (amongst others BDNF, brain derived neurotrophic factor). Part of our research deals with the functional interaction of both systems during the generation of new neurons in the adult mammalian brain. Furthermore, we perform transplantation experiments with cells derived from embryonic stem cells to establish therapeutic interventions for neuropsychiatric/neurodegenerative malfunctions, for example in Chorea Huntington and in spinal cord injury.

Core facility Lipidomics

The Lipidomics facility aims to investigate the dynamics of membrane lipids and bioactive lipids in neurobiological processes using state-of-the-art mass spectrometry techniques. The discovery of lipid signatures of various physiological and/or pathophysiological states, as well as the translation of neurobiological knowledge into quantitative assays for monitoring of changes in the endogenous levels of lipids and bioactive lipids in various tissues and bodily fluids associated with different neuropsychiatric and neurodegenerative diseases, represent the main research activities of the unit.

Lipidomics
Fig. 2: Schematic representation of the quantification workflow of endocannabinoids and related lipids.

The Lipidomics unit collaborates closely with researchers within University Medical Center Mainz, FTN and Institute for Molecular Biology in Mainz, as well as with regional and international medical and academia centers.

The group serves also as a core resource facility of the FTN platform LiPiD, providing quantitative determination of endocannabinoids and other bioactive lipids on a fee-for-service basis. The unit is equipped with modern quantitative mass spectrometer, liquid chromatography systems, high-throughput sample preparation tools, lipidomic software solutions, etc.

For information on collaboration, requests for measurements and internship application please contact Dr. Laura Bindila ( email, Fon: +49 6131 39 25794).

Further information about the Research Group