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Increased striatal lipid peroxidation after intracerebroventricular MPP+ administration to mice
1Department of Neurochemistry, National Institute of Neurology and Neurosurgery, Dr. Manuel Velasco Suàrez, Health Ministry, Mexico 22, D.F.
Abstract:
Mice received different doses intracerebroventricularly of MPP+ (1-methyl-4-phenylpyridinium ion), the active metabolite of MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine), a drug which induces a Parkinson model in rodents. Two indexes of lipid peroxidation were monitored at different times after administration: 1) production of thiobarbituric acid-reactive substances and 2) formation of lipid fluorescence products. A regional-selective overproduction of thiobarbituric acid-reactive substances was observed in corpus striatum and midbrain, but not in frontal cortex, cerebellum nor hippocampus. Enhancement was 70% and 198% at 30 and 60 min. in striatum and 88% at 30 min. in midbrain, when compared with respective controls injected intracerebroventricularly with saline solution. MPP+ also induced lipid fluorescence products formation enhancement in corpus striatum. This increase was dose-dependent in the range of MPP+ doses which induced striatal dopamine depletion. Striatal LFP formation was found increased 24 hr after MPP+ administration (38% vs control), indicating long-lasting lipid peroxidation overproduction. These results suggest that lipid peroxidation might be involved in the neurotoxic effects of MPP+ in vivo.
Insights
MPP+ administration in mice induced lipid peroxidation, evidenced by increased thiobarbituric acid-reactive substances and lipid fluorescence products in specific brain regions. This suggests lipid peroxidation plays a role in MPP+-induced neurotoxicity, relevant to Parkinson
Area of Science:
- Neuroscience
- Toxicology
- Biochemistry
Background:
- MPTP (1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine) is used to create Parkinson's disease models in rodents.
- MPP+ (1-methyl-4-phenylpyridinium ion) is the active metabolite of MPTP.
Purpose of the Study:
- To investigate the role of lipid peroxidation in MPP+-induced neurotoxicity.
- To assess the regional and temporal effects of MPP+ on lipid peroxidation markers in the mouse brain.
Main Methods:
- Mice were administered varying doses of MPP+ intracerebroventricularly.
- Thiobarbituric acid-reactive substances (TBARS) and lipid fluorescence products (LFP) were measured at different time points post-administration.
- Regional brain analysis included corpus striatum, midbrain, frontal cortex, cerebellum, and hippocampus.
Main Results:
- MPP+ caused a selective overproduction of TBARS in the corpus striatum and midbrain.
- Significant increases in TBARS were observed at 30 and 60 minutes post-administration.
- MPP+ also enhanced LFP formation in the corpus striatum in a dose-dependent manner, with elevated levels persisting for 24 hours.
Conclusions:
- MPP+ induces significant lipid peroxidation in specific brain regions relevant to Parkinson's disease pathology.
- The findings suggest that lipid peroxidation is a key mechanism contributing to MPP+-induced neurotoxicity.
- This study highlights the potential involvement of oxidative stress in Parkinsonism.