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LA-ICP-MS bioimaging demonstrated disturbance of metal ions in the brain of Parkinson’s disease model mouse undergoing manganese-enhanced MRI

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Abstract

Manganese-enhanced MRI (MEMRI) is a powerful tool to study neuronal activity and microarchitecture in vivo. Yet the influence of exogenous manganese on the brain of the Parkinson’s disease (PD) model mouse is poorly understood. Laser ablation connected to inductively coupled plasma mass spectrometry (LA-ICP-MS) imaging for tissue section is an ideal tool to simultaneously analyze the metabolism of endogenous metal ions. In this study, DJ-1 knockout PD model mice were subjected to an MnCl2 saline treatment and the distribution of Mn and several other endogenous metal ions in brain regions was assessed by MEMRI and LA-ICP-MS imaging. The results demonstrated that Mn mainly deposited in subcortical regions, such as ventricles, hippocampus (HC), medial preoptic nucleus (MPO), lateral septal nucleus (LS), and ventromedial hypothalamic nucleus (VMH). The enhanced signal-to-noise ratio (S/N) determined by MEMRI for Mn is closely related to the signal in LA-ICP-MS imaging. Significantly, the treatment of MnCl2 disturbs the homeostasis of iron, zinc, copper, and calcium in the DJ-1 mouse, which could result in more severe symptoms of PD. Therefore, the application of MEMRI in the study of neurological disease must be made with caution.

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Abbreviations

Cg/RS:

Cingulate cortex/retrosplenial cortex

M1/2:

Motor cortex

S1:

Primary somatosensory cortex

S2:

Secondary somatosensory cortex

GI/DI:

Granular insular cortex/dysgranular insular cortex

AI:

Agranular insular cortex

Pir:

Piriform cortex

LS:

Lateral septal nucleus

MPO:

Medial preoptic nucleus

HC:

Hippocampal

VMH:

Ventromedial hypothalamic nucleus

SNR:

Substantia nigra, reticular part

CPu:

Caudate-putamen

IL:

Infralimbic cortex

DP:

Dorsal peduncular cortex

VP:

Ventral pallidum

DTT:

Dorsal tenia tecta

Shi:

Septohippocampal nucleus

LV:

Llateral ventricle

PrL:

Prelimbic cortex

CB:

Cell bridges of the ventral striatum

SI:

Substantia innominata

PD:

Parkinson’s disease

MEMRI:

Manganese-enhanced magnetic resonance imaging

LA-ICP-MS:

Laser ablation connected to inductively coupled plasma mass spectrometry

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Acknowledgements

We thank Professor Lanqun Mao from Bei**g Normal University for inspiring discussion during this work, and Prof Zongxiu Nie from the Institute of Chemistry, Chinese Academy of Sciences for their cryo-cutting devices.

Funding

National Natural Science Foundation of China (Grant Nos. 21790390, 21790392, 22004121, and 21927804). China Postdoctoral Science Foundation, Grant No. 2020M680675, for T. Fang.

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Author notes

  1. Tiantian Fang and Wei Chen contributed equally to this work.

Authors and Affiliations

  1. Bei**g National Laboratory for Molecular Sciences; CAS Research/Education Center for Excellence in Molecular Sciences, National Centre for Mass Spectrometry in Bei**g, CAS Key Laboratory of Analytical Chemistry for Living Biosystems, Institute of Chemistry, Chinese Academy of Sciences, Bei**g, 100190, People’s Republic of China

    Tiantian Fang, Yiyu Cheng, Yanyan Zhang, Qun Luo, Fuyi Wang & Yao Zhao

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

    Wei Chen & Hao Lei

  3. University of Chinese Academy of Sciences, Bei**g, 100049, People’s Republic of China

    Wei Chen, Qun Luo, Fuyi Wang & Hao Lei

  4. Key Laboratory of Hubei Province for Coal Conversion and New Carbon Materials, School of Chemistry and Chemical Engineering, Wuhan University of Science and Technology, Wuhan, Hubei, 430081, People’s Republic of China

    Yiyu Cheng & Kui Wu

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Correspondence to Hao Lei or Yao Zhao.

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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).

Competing interests

The authors declare no competing interests.

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, maintained at Innovation Academy for Precision Measurement Science and Technology, Chinese Academy of Sciences.

Statement on animal welfare

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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Fang, T., Chen, W., Cheng, Y. et al. LA-ICP-MS bioimaging demonstrated disturbance of metal ions in the brain of Parkinson’s disease model mouse undergoing manganese-enhanced MRI. Anal Bioanal Chem 414, 5561–5571 (2022). https://doi.org/10.1007/s00216-022-03994-9

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