In vivo magnetic resonance approach to trimethyltin induced neurodegeneration in rats

Abstract

Trimethyltin (TMT) is commonly used to induce neurodegeneration in mice and rats; however, only scarce data of in vivo magnetic resonance (MR) spectroscopy and imaging characterizing TMT neurotoxicity are available. Our aim was to assess brain metabolite changes and brain atrophy by in vivo MR in the rat model of neurodegeneration induced by TMT. Adult male Wistar rats exposed to TMT (8mg/kg, i.p.) were used in the study. Proton MRS was applied on the dorsal hippocampus to reveal changes in neurochemical profile, and MR imaging was used to assess the volume of the entire hippocampus, ventricles and whole brain. Hippocampal levels of N-acetylaspartate (NAA), glutamate (Glu), total creatine (tCr) and taurine (Tau) significantly decreased, while the levels of myo-Inositol (mIns) and glutamine (Gln) significantly increased in TMT treated rats compared to controls. No changes in choline metabolites (tCho), glutathione (GSH), and GABA were observed. MR volumetry revealed a substantial loss of hippocampal mass, cerebral volume shrinkage and ventricular enlargement in the TMT treated group in comparison to the control group. To the best of our knowledge, this is the first study characterizing TMT induced neurodegeneration in the rat by in vivo MRS. Our findings suggest that TMT exposed rats may serve as a reliable animal model of neurodegeneration and MR based parameters could serve as potential in vivo biomarkers of therapeutic response.

Keywords: Brain atrophy; In vivo MRS; MRI volumetry; Neurodegeneration; Rat hippocampus; Trimethyltin neurotoxicity.