Related Experiment Video
Updated: Aug 11, 2026
Behavioral Assessments of Spontaneous Locomotion in a Murine MPTP-induced Parkinson's Disease Model
Published on: January 7, 2019
H MRS identifies lactate rise in the striatum of MPTP-treated C57BL/6 mice
Keiko Koga1, Atsushi Mori, Satoshi Ohashi
1Laboratory of Bioenergetics Research, Tokushima Research Institute, Otsuka Pharmaceutical Co. Ltd, Tokushima 771-0192, Japan.
Abstract:
Mitochondrial dysfunction has been implicated in the death of nigrostriatal dopaminergic neurons in 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP)-treated experimental models of Parkinson's disease (PD). Here we utilized proton magnetic resonance spectroscopy ((1)H MRS) to identify changes in energy metabolism in the striatum of MPTP-treated C57BL/6 mice. Remarkable increases in lactate/creatine (Lac/Cr) ratio were observed at 2 h and then quickly returned to about the basal level by 7 h after injection of MPTP. Neurochemical and Western blot analyses revealed that dopamine contents and protein levels of tyrosine hydroxylase and dopamine transporter in the striatum were profoundly decreased at 3 days after MPTP treatment. Pretreatment with deprenyl, a monoamine oxidase B inhibitor, or GBR-12909, a dopamine uptake inhibitor, almost completely attenuated both the increases in striatal Lac/Cr ratio and the subsequent loss of dopaminergic nerve terminals in MPTP-treated mice. The present study indicates that (1)H MRS is a sensitive measure of biochemical alterations of the brain in a mouse model of PD, and further shows that the increases in striatal Lac/Cr ratio induced by MPTP may be associated with mitochondrial energy crisis, followed by dopaminergic neurotoxicity.
Insights
Proton magnetic resonance spectroscopy ((1)H MRS) detected early energy metabolism changes in a Parkinson
Area of Science:
- Neuroscience
- Biochemistry
- Medical Imaging
Background:
- Mitochondrial dysfunction is linked to dopaminergic neuron loss in Parkinson's disease (PD) models.
- The 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model mimics PD neurodegeneration.
- Understanding early metabolic changes is crucial for PD research.
Purpose of the Study:
- To use proton magnetic resonance spectroscopy ((1)H MRS) to detect early energy metabolism alterations in the striatum of MPTP-treated mice.
- To investigate the relationship between metabolic changes and dopaminergic neurotoxicity in a PD model.
- To assess the neuroprotective effects of deprenyl and GBR-12909 on MPTP-induced neurotoxicity.
Main Methods:
- MPTP was administered to C57BL/6 mice to induce Parkinson's disease-like pathology.
- Proton magnetic resonance spectroscopy ((1)H MRS) was used to measure the lactate/creatine (Lac/Cr) ratio in the striatum.
- Neurochemical assays and Western blot analyses were performed to quantify dopamine levels and related proteins.
- Mice were pretreated with deprenyl or GBR-12909 to evaluate neuroprotective effects.
Main Results:
- MPTP treatment caused a rapid, transient increase in the striatal Lac/Cr ratio, indicating altered energy metabolism.
- Dopamine content and tyrosine hydroxylase/dopamine transporter levels significantly decreased in the striatum by 3 days post-MPTP.
- Deprenyl and GBR-12909 pretreatment attenuated both the metabolic changes and the loss of dopaminergic terminals.
Conclusions:
- (1)H MRS is a sensitive tool for detecting biochemical brain alterations in PD models.
- MPTP-induced increases in striatal Lac/Cr ratio are associated with mitochondrial energy crisis and subsequent dopaminergic neurotoxicity.
- Pharmacological interventions targeting monoamine oxidase B or dopamine uptake can protect against MPTP-induced neurodegeneration.
