Accelaration of MPTP-induced neurotoxicity in obese mice: nNOS phosphorylation and MnSOD activity

초록

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 12 weeks, single intraperitoneal dose of MPTP were administered and biochemical assays were conducted at 24hrs after MPTP administration. After 12 weeks, the plasma NOx (nitrate and nitrite) level in obese mice was higher than that of lean mice indicating the production of systemic inflammation. The striatal dopamine content was significantly decreased in obese mice by MPTP compared with that of lean mice. As the phosphorylation of nNOS, the trend of increase in phosphorylation of nNOS in obese mice was observed. Furthermore, the mitochondrial superoxide dismutase (Mn-SOD) was inhibited only in obese mice. Combined our present and previous (modest obese model) results, the mechanisms of increased vulnerability of dopaminergic system against the MPTP in obese mice considering the phosphorylation of nNOS and alteration of Mn-SOD activity will be discussed.