EFFECTS OF HIGH FAT DIET-INDUCED OBESITY ON NEURO-DEGENERATION IN MPTP-TREATED MICE

초록

Currently, obesity is considered as a systemic inflammatory condition. In a previous epidemiologic study, midlife adiposity is associated with an elevated risk of future Parkinson’s disease. However, the effects of obesity on the vulnerability of central dopaminergic system against exposure to 1-methy1-4-phenyl-1,2,3,6-tetrahydropyridin(MPTP) are not fully defined. Furthermore, although the neuronal nitric oxide(NO) signaling is closely associated with the food intake and dopamine homeostasis , the effects of alteration of NO signal on the susceptibility of dopaminergic neurons to neurotoxins are not determined. Recently, it was reported that the phosphorylation of neuronal NO synthase(Nnos) produced the decreased activity of Nnos. In this study, we evaluated the susceptibility of obese mice to acute dopaminergic toxicity of MPTP after induction of obesity by high-fat diet for 8 weeks and subsequent subtoxic dose of MPTP. After 8 weeks, the plasma Nox level in obse mice was higher than that of lean mice indicating the production of systemic inflammation. The decrease in striatal dopamine, TH and MAP-2 content and nigral Mn-SOD level were severe in obese mice by MPTP as compared with lean mice. The increase in phosphorylation of striatal nNOS in obese mice with MPTP was observed. Furthermore, the nigral nitrotyrosine level in obese mice with MPTP was higher than that in lean mice. Combined our present, the mechanisms of increased vulnerability of dopaminergic system against the MPTP in obese mice considering the phosphorylation of Nnos and elevation of ROS/RNS will be discussed(Supported by BK-21)