Dopaminergic dysfunction and molecular pathways to selective neurodegeneration: from mouse models to Parkinson disease

Coordinator:		Prof. Dr. Birgit Liss; Prof. Dr. Jochen Roeper
Institution:		Institute of Applied Physiology, University of Ulm
Homepage:		http://www.uni-ulm.de/med/

Neurons that release the transmitter dopamine are nor equally affected by the progressive death in Parkinson’s disease (PD) and its animal models. The cause for this differential vulnerability of dopamine neurons to PD-trigger factors is still unclear.

Aim of this project is, to define functional and molecular differences between distinct types of dopamine neurons with differential vulnerability to disease. In particular we analyze, how PD-triggers (e.g. so-called metabolic stress, induced by PARK-gene mutations or distinct drugs) selectively change activity and gene-expression of distinct dopamine neurons, and finally lead to cell death.

Dopamine-autoreceptors and ion channels are from particular interest for us, as they not only directly define activity-patterns of neurons, but also as for some of proteins a role for PD and its mouse models has already been shown.

The results of our studies lead to a better understanding of the mechanisms of selective degeneration of dopamine neurons in PD. Understanding the roles of PD-triggers in interplay with ion channels can identify novel molecular mechanisms of the PD process, and potentially novel therapeutic targets. Our studies of dopamine-receptors are also important in context of side effects of unspecific dopamine-mimetic therapies.

This study is carried out in close cooperation of the research group Liss at Ulm University
(in particular cell specific RNA- und DNA-analysis of neurons form mice and men, as well as in vitro electrophysiology and tracing) and the research group  Roeper, University of Frankfurt am Main (in particular in vivo und in vitro electrophysiology, viral transfection, tracing and immunocytochemistry). Genetic mouse models are provided within the NGFN network (TP Auburger, TP Haas/Winklhofer, TP Wurst). Behavioural analysis is carried out in cooperation with the NGFN Mousesclinic (Hrabe de Angelis).

Within this funding-network, we could further define the specific roles of distinct subtypes of ion channels for the function of dopamine neurons in health and PD.

For more information, please see also: http://www.ngfn.de/de/parkinson_liss_und_roeper.html