Mapping the alterations in glutamate with GluCEST MRI in a mouse model of dopamine deficiency

摘要

Glutamate Chemical Exchange Saturation Transfer (GluCEST) MRI was used to measure metabolic changes in mice treated with 1-methyl-4-phenyl1,2,3,6-tetrahydropyridine (MPTP) by mapping regional cerebral glutamate. The GluCEST contrast following MPTP treatment was correlated with ¹H MR spectroscopy, motor function and immunohistochemical measures. GluCEST contrast was found to be significantly higher in the striatum and motor cortex of mice treated with MPTP than in controls (p<0.001), which was confirmed by localized ¹H MR spectroscopy. Elevated striatal GluCEST was positively associated with local astrogliosis measured by immunohistochemistry for glial fibrillary acidic protein (GFAP). Additionally, a negative correlation was found between the GluCEST of striatum (R = −0.705, p<0.001) and motor cortex (R = −0.617, p<0.01) with motor function measured by the four limb grip strength test, suggesting a role of elevated glutamate in the abnormal cerebral motor function regulation. GluCEST contrast and GFAP staining were unaltered in the thalamus indicating glutamate elevation was localized to striatum and possibly motor cortex. These findings suggest that in addition to measuring spatial changes in glutamate, GluCEST may serve as an in vivo biomarker of metabolic and functional changes that may be applied to the assessment of a broad range of neuropathologies.