Work Package 2

Environmental risk and protective factors in genetic rodent models of affective disorders

Dr. Markus Wöhr1, Prof. Dr. Holger Garn2, Prof. Dr. Rainer Schwarting1
1University of Marburg, Department of Experimental and Biological Psychology, Behavioural Neuroscience

2University of Marburg, Institute of Laboratory Medicine and Pathobiochemistry – Molecular Diagnostics, Biomedical Research Centre (BMFZ)

 

This work package (WP2) serves as the animal backbone study for the entire FOR. Compared to human research on affective disorders, which has to rely on correlative and quasi-experimental approaches, genetic and environmental factors can be fully experimentally controlled and systemically varied in animal research. Therefore, appropriate animal models for core symptoms of human affective disorders are of immense translational relevance as they allow, for example, to specifically apply environmental risk and protective factors during defined time windows, study their short- and long-term outcomes, and investigate interactions with defined genes in genetically modified rodents. WP2 follows the well-grounded hypotheses that gene x environment (GxE) interactions trigger the development of affective disorders. Genetic factors in focus are two recently identified risk genes, i.e. Cacna1c and Ncan, while maltreatment and beneficial environment will be studied as important environmental conditions that specifically act in windows of opportunity during development. WP2 has the following major goals: Initially, we will perform deep and longitudinal behavioural phenotyping of newly generated Cacna1c and Ncan genetic rat models with specific emphasis on measures relevant for major depressive disorder (MDD) and bipolar disorder (BD). Secondly, we will analyse how environmental factors affect these phenotypes, focusing on post-weaning social isolation as maltreatment, and social and physical enrichment as beneficial environment. We expect that maltreatment enhances deficits in the Cacna1c and Ncan rats, while beneficial environment may prevent the development of a phenotype relevant to affective disorders. Thirdly, we will study neurobiological mechanisms underlying GxE interactions resulting in MDD- and BD-related behavioural phenotypes. Specifically, we will assess local changes in functional brain activation patterns, biogenic amine activity, neuromorphometric measures, and hippocampal neurogenesis. Markers of neuroinflammation, including proinflammatory cytokines and chemokines, and marks of epigenetic regulation, i.e. DNA methylation and histone modifications of candidate genes for affective disorders, will be determined. Furthermore, we will establish a tissue bank to provide our collaborators with relevant tissue material for studies on miRNAs (WP3), neuronal morphology (WP3), in-vitro electrophysiology (WP3), and cellular stress (WP4). Finally, GxE interactions on brain structure and function as well as inflammatory and epigenetic markers will be compared to analogous measures in humans (CP1/WP1/WP5).

Project Manager

Dr. Markus Wöhr

Dr. Markus Wöhr

PD Dr. Holger Garn

PD Dr. Holger Garn

Prof. Dr. Rainer Schwarting

Prof. Dr. Rainer Schwarting

Employees

Dipl.-Psych. Moria Braun

Dipl.-Psych. Moria Braun

Theresa Kisko, M.Sc.

Theresa Kisko, M.Sc.

Tobias Redecker,  M.Sc. Psychology

Tobias Redecker, M.Sc. Psychology

Sophia Bernhard, MTA