Altered brain connectivity in a transgenic mouse which over-express human hydrolase hMTH1 following an oxidative stimulus: a rs-fMRI and DTI study

Altered brain connectivity in a transgenic mouse which over-express human hydrolase hMTH1 following an oxidative stimulus: a rs-fMRI and DTI study Introduction The role of the oxidative stress in the pathogenesis of neurodegeneration is well known. The Human MutT homologue (hMTH1) is a hydrolase able to protect nucleic acids from oxidative damage. Interestingly, transgenic mice which overexpress the human MTH1 gene (hMTH1‐Tg) are protected from neurodegeneration and motor impairment. Aims To understand if the over-expression of hMTH1 is able to counteract the effects of a chronic exposure to an oxidant, like Paraquat. Methods Male C57bl6 mice, wild-type and hMTH1-Tg, were analysed by rs-fMRI and DTI before and after a chronic treatment with Paraquat. Experiments were performed on a Pharmascan Bruker (Ettlingen, DE) system operating at 7T equipped with a cryo-probe. Mouse brain resting state fMRI was studied with seed-based analysis. In the DTI study an EPI sequence with 30 direction gradient was used. The diffusivity values (fractional anisotropy, FA and mean diffusivity, MD) were derived from the tensor. Results Our preliminary seed-based analysis shows differences in the functional networks of the wt and the hMTH1-Tg mice after exposure to the oxidant compound. DTI analysis reveals region specific alterations of FA and MD which differ in the two group of animals after Paraquat exposure. Analysis in other relevant brain areas are in progress. Discussion and Conclusion Taken together these results show a diverse brain vulnerability of the transgenic mice to the Paraquat exposure, compared to wt and help to deepen insights into the possible mechanisms of action of the hMTH1 over-expression on brain function and structure.