Untersuchungen von Motorik, Kognition und Verhalten bei Mausmodellen von Motoneuronerkrankungen

Amyotrophic lateral sclerosis (ALS) is a progressive neurodegenerative disease, characterized by degeneration of upper and lower motor neurons. Most cases (90%) are classified as sporadic ALS, 10 % are inherited and referred to as familial ALS. In about 15-20% of those cases, a mutation in the gene encoding the antioxidant enzyme Cu/Zn dismutase 1 (SOD1) has been found. There is an increasing recognition of clinical overlap between frontotemporal dementia (FTD) and ALS in some ALS patients. Following the current discussion of ALS and FTD overlap, the aim of the current study was to explore the effects of mutations in mouse models. The investigated effects refer to motor functions, behaviour, and cognition. The classical ALS mouse model SOD1, the Cra1 and the double-transgenic Cra1/SOD1 animals, were to be investigated on their validity of ALS models. Age matched wild type animals with the identical genetic background served as control as well as the P301L model. This is a transgenic mouse, characterized by a mutation in the protein tau, and therefore a FTD model. The behavioural tests were complemented by histomorphometric characterisation of the musculus quadrizeps. The most important results concerned the Cra1 animals. They showed deficits in agility, motor coordination and muscular strength, distinct hyperactivity, no disturbance of exploration and anxiety as P301L mice as well as a normal cognition, no neurogenic changes in skeletal muscles. These results suggest that Cra1 mice are neither an ALS model nor a tauopathie model. Therefore the present classification of the Cra1 mice, in terms of an ALS model, has to be challenged. Similar characteristics with regard to hyperactivity and deficits in motor coordination in Cra1 mice can be found in mouse models with neurodegeneration at the corpus striatum. Therefore, I can conclude that Cra1 mice resemble an animal model with degenerations in the striatum