Differences in brain pathological changes between rotenone and 6-hydroxydopamine Parkinson’s disease models

Abstract

Rotenone and 6-hydroxydopamine are two drugs commonly used to generate Parkinson’s disease animal models. They not only achieve degenerative changes of dopaminergic neurons in the substantia nigra, but also satisfy the requirements for iron deposition. However, few studies have compared the characteristics of these two models by magnetic resonance imaging. In this study, rat models of Parkinson’s disease were generated by injection of 3 μg rotenone or 10 μg 6-hydroxydopamine into the right substantia nigra. At 1, 2, 4, and 6 weeks after injection, coronal whole-brain T2-weighted imaging, transverse whole-brain T2-weighted imaging, and coronal diffusion tensor weighted imaging were conducted to measure fractional anisotropy and T2* values at the injury site. The fractional anisotropy value on the right side of the substantia nigra was remarkably lower at 6 weeks than at other time points in the rotenone group. In the 6-hydroxydopamine group, the fractional anisotropy value was decreased, but T2* values were increased on the right side of the substantia nigra at 1 week. Our findings confirm that the 6-hydroxydopamine-induced model is suitable for studying dopaminergic neurons over short periods, while the rotenone-induced model may be appropriate for studying the pathological and physiological processes of Parkinson’s disease over long periods.

Keywords

• nerve regeneration; fractional anisotropy; T2FNx01; rotenone; 6-hydroxydopamine; Parkinson′s disease; magnetic resonance imaging; diffusion tensor imaging; dopaminergic neurons; neural regeneration