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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

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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.

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Data availability

The data set will be available upon request.

Abbreviations

1H-MRS:

Proton magnetic resonance spectroscopy

MRI:

Magnetic resonance imaging

MALDI-MSI:

Matrix-assisted laser desorption/ionization mass spectrometry imaging

6-OHDA:

6-Hydroxydopamine

MPTP:

1-Methyl-4-phenyl-1,2,3,6-tetrahydropyridine

AD:

Alzheimer’s disease

PD:

Parkinson’s disease

WT:

Wild-type

CRLB:

Cramér–Rao lower bound

tCr:

Total creatine

Cr:

Creatine

PCr:

Phosphocreatine

NAA:

N-Acetyl aspartate

Tau:

Taurine

Cys:

Cysteine

DA:

Dopaminergic

Gln:

Glutamine

Glu:

Glutamate

Gly:

Glycine

GSH:

Glutathione

MFB:

Medial forebrain bundles

mPFC:

Medial prefrontal cortex

SNc:

Substantia nigra pars compacta

FrA:

Frontal association cortex

ROI:

Region of interest

SNR:

Signal-to-noise ratio

FWHM:

Full width at half maximum

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Funding

This work was supported by the National Natural Science Foundation of China (grant numbers 21790392 and 21790390).

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Author notes

  1. Wei Chen and Huihui Liu contributed equally to this work.

Authors and Affiliations

  1. State Key Laboratory of Magnetic Resonance and Atomic and Molecular Physics, Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences, 30# Xiaohongshan West, Wuhan, 430071, Hubei, People’s Republic of China

    Wei Chen, Sijie Liu, Yan Kang & Hao Lei

  2. University of Chinese Academy of Sciences, Beijing, 100049, People’s Republic of China

    Wei Chen, Sijie Liu, Zongxiu Nie & Hao Lei

  3. Beijing National Laboratory for Molecular Sciences, Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Zhongguancun North First, Street 2, Beijing, 100190, China

    Huihui Liu & Zongxiu Nie

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  1. Wei Chen
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Correspondence to Zongxiu Nie or Hao Lei.

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Ethics approval

All animal experiments were approved by the Institutional Animal Care and Use Committee of Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences (protocol number: APM20028A).

Source of biological material

DJ-1 knockout mice (C57BL/6 J background) were kindly provided by the Experimental Animal Center of Peking University and bred and maintained at the Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences.

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All animal experiments were performed according to the National Institutes of Health (NIH) Guide for the Care and Use of Laboratory Animals. All efforts were made to minimize the number of animals used and their suffering.

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Chen, W., Liu, H., Liu, S. et al. 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. Anal Bioanal Chem 414, 7977–7987 (2022). https://doi.org/10.1007/s00216-022-04341-8

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