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Searching for gene-environment interactions leading to pathogenic synergy, this thesis examines the neuropathological effects of an intoxication with the prototypical complex I inhibitor annonacin in a transgenic FTDP-17 mouse model. This work aimed to test, whether annonacin leads to a neuronal accumulation of hyperphosphorylated tau in vivo, which is the characteristical hallmark of FTDP-17 and other tauopathies. Furthermore it aimed to resolve, whether the interaction of annonacin and a genetic factor leads to an increase in tau pathology and whether treatment with annonacin is accompanied by neuronal death and microglial reaction. To clarify these questions we treated mice overexpressing the longest human tau isoform with the R406W mutation and wildtype mice with annonacin (6 mg/kg/d or 9 mg/kg/d) or vehicle via subcutaneous administration with osmotic mini-pumps for a three-day period. Thereafter immunohistochemical staining of the brain tissue was done with antibodies against phosphorylated tau, neurons and glial cells. Quantification of neurons und glial cells in the different brain regions (frontal and parietal cortex, hippocampus, amygdala) was conducted by stereological cell counting und optical density measurement. In comparison to wildtype mice, the expression of the transgene in R406W+/+ mice was sufficient to cause somatodentritic accumulation of hyperphosphorylated tau. Administration of annonacin led to a dose-dependent increase of somatodentritic phospho-tau accumulation in R406W+/+ mice, while there was no effect in R406W-/- mice. This increase in tau pathology was determined by an increase of phospho-tau positive neurons in the frontal und parietal cortex and by an increased optical density of phospho-tau positive neurons in the CA2/3 region of the hippocampus. In the amygdala, annonacin exposure had no significant additional effect on phospho-tau labeling. Immunohistochemical staining of neurons using the anti-NeuN antibody revealed that there is a significantly lower number of neurons in all brain regions examined in R406W+/+ mice as compared to R406W-/- mice. However annonacin treatment had no significant influence on neuronal numbers in the different treatment groups und genotypes. In the same way, annonacin did not cause significant alteration in the number of microglia or astrocytes of either transgenic or wildtype mice. In summary, this work has shown that a three-day exposure with annonacin is sufficient to cause a dose-dependent increase of somatodentritic accumulation of phospho-tau in R406W-transgenic mice. This demonstrates that an environmental toxin is able to change the course of a tauopathy determined by a genetic factor by increasing tau pathology in synergism with the genetic defect. It should be the aim of further studies to elucidate the relevance of further globally distributed environmental toxins in the pathogenesis of tauopathies as well as the exact mechanisms which lead to tau pathology. This knowledge will be essential for the understanding of the pathogenesis of these diseases and for the development of prophylactic and therapeutic strategies for the treatment of tauopathies. The FTDP-17 mouse model used in this study can be applied in further studies and might give insights, which are relevant not only for FTDP-17 but also for other tauopathies of genetic or sporadic origin.