Altered prefrontal neurochemistry in the DJ-1 knockout mouse model of Parkinson's disease: complementary semi-quantitative analyses with in vivo magnetic resonance spectroscopy and MALDI-MSI.

Abstract

In vivo proton magnetic resonance spectroscopy (1H-MRS) and matrix-assisted laser desorption/ionization mass spectrometry imaging (MALDI-MSI) are two semi-quantitative analytical methods commonly used in neurochemical research. In this study, the two methods were used complementarily, in parallel, to investigate neurochemical perturbations in the medial prefrontal cortex (mPFC) of 9-month-old DJ-1 knockout mice, a well-established transgenic model for Parkinson's diseases. Convergingly, the results obtained with the two methods demonstrated that, compared with the wild-type (WT) mice, the DJ-1 knockout mice had significantly increased glutathione (GSH) level and GSH/glutamate (Glu) ratio in the mPFC, which likely presented an astrocytic compensatory mechanism in response to elevated regional oxidative stress induced by the loss of DJ-1 function. The results from this study also highlighted (1) the need to be cautious when interpreting the in vivo 1H-MRS results obtained from aged transgenic animals, in which the concentration of internal reference, being whether water or total creatine, could no longer be assumed to be the same as that in the age-matched WT animals, and (2) the necessity and importance of complementary analyses with more than one method under such circumstances.