Donders Institute for Brain, Cognition and Behaviour
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Thesis defense Elisavet Kyriakou (Donders series 423)

13 February 2020

Promotor:  prof. dr. J. Homberg, prof. dr. B. Roozendaal
Co-promotor: dr. J. van der Harst (Noldus Information Technology B.V.)

Unravelling the behavioural and molecular hallmarks of Spinocerebellar Ataxia type 17 (SCA17). Studies on a transgenic rat model

Spinocerebellar Ataxia type 17 (SCA17) is a rare and severe autosomal-dominant neurological disorder with currently no available cure. The clinical description consists of progressive uncoordinated gait, cognitive dysfunctions, dementia, involuntary movements, including chorea, spasticity, parkinsonism, dystonia and neuropsychiatric symptoms. SCA17 is caused by a CAG/CAA repeat expansion of 45 or more in the TATA-box protein (TBP) gene. The work presented in this thesis aims at the validation of a relatively new animal model for the detection of early onset symptoms of SCA17 and suggests several directions for future research. Additionally, this work highlights the importance of a holistic approach when validating the symptoms of SCA17 at a preclinical level, to cover the complexity of all disease features and symptomatology. Such an approach contributes significantly to our understanding of the neuropathological mechanisms underlying SCA17 and can help to develop valuable animal experiments for subsequent therapeutic studies. New information about the onset and development of several disease symptoms from motoric and psychiatric phenotypes to molecular changes in the brain of the SCA17 rat model were presented. The results can be useful for identifying suitable intervention time points when designing innovative therapeutic studies in the future, which ultimately will hopefully contribute to the development of successful therapies for this devastating neurodegenerative disease.