Effects of high fat diet-induced obesity on neurodegeneration 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-methyl-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 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-far diet for 8 weeks, subtoxic dose of MPTP were administered and biochemical assays were conducted at 7 days after MPTP administration. After 8 weeks, the plasma NOx level in obese mice was higher than that of lean mice indicating the production of systemic inflammation. The decrease in striatal dopamine content was severe in obese mice by MPTP compared with that of lean mice. As the phosphorylation of nNOS, the increase in phosphorylation fo nNOS in obese mice with MPTP was observed. Furthermore, the nitrosine level in obese mice with MPTP was higher than 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.