(Coordination: Eckart Altenmüller)

Many neurological illnesses manifest predominantly in motor disturbances. With the introduction of molecular techniques, by means of modern neurophysiological and imaging methods, and by development of suitable animal models the pathophysiology of these illnesses has been successfully elucidated and new therapeutic concepts have been developed.  

The ZSN main focus “Disturbances in motor systems, models and clinic” was formed to emphasise the linking up of numerous neuroscientific groups in Hannover working on this topic. A major advantage of the ZSN is that several groups work cooperatively on different organisational levels of the nervous system, whereby basal ganglia illnesses, (Parkinson´s disease, Dystonia), motor neuron diseases (Amyotrophic lateral sclerosis) and Demyelinating illnesses are most prominent research topics.  

Parkinson´s disease serves as an example of the joint work of various groups of the ZSN on a system. The group of Grothe (Neuroanatomy of the MHH) is investigating neural dopamine stem cells on a molecular-cellular level. The stem cells are genetically manipulated and characterised in vitro. Afterwards the cells are implanted in a-rat model of Parkinson’s disease. The anatomical and functional integration of these cells are tested by means of morphological and behavioural investigations. The group of Dengler (Neurological Clinic of the MHH) is working diagnostically on subtle neuropsychological deficits of emotional perception of Parkinson´s patients. The group of Krauss and Schwabe (Neurosurgery of the MHH) is searching for new goals for the deep brain stimulation in animal models of Parkinson´s disease. Furthermore, mechanisms of action of deep brain stimulation of various goals in a clinical context in the case of patients with Parkinson´s disease, Tourette´s syndrome and Dystonia are being investigated (Krauss, Neurosurgery).  

The pathophysiology and therapy of Dystonia is a further question linking numerous groups of the main focus. The groups of Dengler and Dressler (Neurology of the MHH), Altenmüller (HMTH), Bleich (Dept. of Psychiatry), Krauss (Neurosurgery of the MHH), together with Lanfermann (Neuroradiology of the MHH) are working on neuropsychological, neurogenetic, neurophysiological and neuro-morphological features in patients with Dystonia. Here action-induced dystonia, in particular writer’s cramp and musician’s cramp are in the focus.  

In several groups the mechanisms of neurodegeneration and regeneration of central and peripheral motor systems are intensively researched. In particular, the pathogenesis and therapy of motor neuron illnesses is investigated. Here, the close interlocking of molecular and neurophysiological analyses as well as of animal models with clinical aspects and applications is emphasized. The groups of Dengler and Petri (Neurology of the MHH) are researching the pathomechanisms and therapy options of amyotrophic lateral sclerosis (ALS). Investigations into human post mortem brain- and bone marrow from the back of ALS patients are the main focus, whereby the aim is to characterise neurotransmitter receptors and to ascertain those factors involved in regulating oxidative stress and inflammatory mechanisms. The working group under PD. Dr. Claus concentrates on spinal muscle atrophy in children. Alongside cellular mechanisms of pathogenesis in cooperation with the working group Hildebrandt it is being investigated as to how far polysialic acids promote the plasticity of motor neurons.  

The role of neuromuscular end-plates in both diseases is also being analysed in this main focus. In the group of Dengler together with the groups of Grothe and Claus the effects of different subunit formations of receptors are functionally characterised. Furthermore, studies on the transgenic mouse model of the ALS as well as on embryonic motor-neuron precursor cultures from transgenic and non-transgenic animals for testing potential neuroprotective substances are being carried out. Lastly, in the working groups under Krampfl and Bicker work is being carried out to create motor neurons for transplants out of precursory cells. 

Further important facets of this main focus which should be named are demyelinating inflammatory diseases of the motor system with the prototypical disease multiple sclerosis. Here investigations into animal models and clinical research are closely interlocked: fundamental mechanisms are investigated with different animal models by the groups of Baumgärtner (Pathology TiHo), Tipold (Small Animal Clinic, TiHo) and Stangel (Neurology, MHH). The research is carried out complementarily in toxic (induced by cuprizone) and viral (Theiler virus) mouse models as well as in a dog model (canine distemper). With respect to the mouse models, various genetically manipulated mice are used to characterise the influence of individual molecules on demyelinisation and remyelinisation. The investigations are complemented in all working groups by work on cell cultures with various glial cells (oligodendrozytes, microglia, astrozytes). In cooperation with the working group of Bicker (Physiology and Cell Biology, TiHo) the effect of nitrogen monoxide (NO) is being investigated. The central focus is on mechanisms of tissue destruction as well as on regeneration. By discovering fundamental mechanisms, the aim is to develop new therapeutic strategies and to test these in the animal model. Clinical therapy studies of phase II and III are being carried out on patients with multiple sclerosis in Neurology (Stangel, MHH). Due to numerous scientific and methodical mutual questions with other working groups with regard to content, various co-operations have resulted with other working groups of the ZSN (Löscher, Gerardy-Schahn, Hildebrand, Grothe, Claus, and Petri).  

Finally, also the groups focussing on peripheral nerves should be highlighted. For bridging peripheral nerve lesions after substance loss biohybrid implants are being developed. The substrate basis in this case is polysialic acid which serves as a framework and populated with genetically modified Schwann cells functions as a nerve bridge. This project, jointly supported by the groups Gerardy-Schahn and Grothe, is the theme of the DFG-Research group involved in this main focus.