Diffusion Kurtosis Imaging Detects Microstructural Changes in a Methamphetamine-Induced Mouse Model of Parkinson’s Disease

Abstract

Methamphetamine (METH) abuse is known to increase the risk of Parkinson’s disease (PD) due to its dopaminergic neurotoxicity. This is the rationale for the METH model of PD developed by toxic METH dosing (10 mg/kg four times every 2 h) which features robust neurodegeneration and typical motor impairment in mice. In this study, we used diffusion kurtosis imaging to reveal microstructural brain changes caused by METH-induced neurodegeneration. The METH-treated mice and saline-treated controls underwent diffusion kurtosis imaging scanning using the Bruker Avance 9.4 Tesla MRI system at two time-points: 5 days and 1 month to capture both early and late changes induced by METH. At 5 days, we found a decrease in kurtosis in substantia nigra, striatum and sensorimotor cortex, which is likely to indicate loss of DAergic neurons. At 1 month, we found an increase of kurtosis in striatum and sensorimotor cortex and hippocampus, which may reflect certain recovery processes. Furthermore, we performed tract-based spatial statistics analysis in the white matter and at 1 month, we observed increased kurtosis in ventral nucleus of the lateral lemniscus and some of the lateral thalamic nuclei. No changes were present at the early stage. This study confirms the ability of diffusion kurtosis imaging to detect microstructural pathological processes in both grey and white matter in the METH model of PD. The exact mechanisms underlying the kurtosis changes remain to be elucidated but kurtosis seems to be a valuable biomarker for tracking microstructural brain changes in PD and potentially other neurodegenerative disorders.

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Acknowledgments

The authors are grateful to Dr. Peter Latta for his valuable technical support and help with the MRI scanning and a professional data analyst Ms. Daniela Kuruczova for her advice on statistical analysis. The behavioural apparatuses for the challenging beam traversal and grid test were kindly provided by Jiri Kucera, Environmental Measuring Systems, Brno, Czech Republic.

Funding

This study was performed at Masaryk University as part of the project “Pharmacological research in the field of pharmacokinetics, neuropsychopharmacology and oncology”, number MUNI/A/1550/2018, with the support of the Specific University Research Grant, as provided by the Ministry of Education, Youth and Sports of the Czech Republic in the year 2019 and also supported by funds from the Faculty of Medicine MU to junior researcher Jana Ruda-Kucerova. The work was also supported from European Regional Development Fund-Project “National infrastructure for biological and medical imaging” (No. CZ.02.1.01/0.0/0.0/16_013/0001775). We acknowledge the core facility MAFIL of CEITEC and the MR unit and the animal facility (CZ62760225) of ISI CAS, both supported by the Czech-BioImaging large RI project (LM2015062 funded by MEYS CR), for their support with obtaining scientific data presented in this paper. Nikoletta Szabo was supported by NAP 2.0 (2017-1.2.1-NKP-2017-00002), EFOP-3.6.1-16-2016-00008 and KTIA_13_NAP-A-II/20. The ISI CAS support was further co-financed by MEYS CR and EC (CZ.1.05/2.1.00/01.0017) and by the CAS (RVO:68081731).

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Arab, A., Ruda-Kucerova, J., Minsterova, A. et al. Diffusion Kurtosis Imaging Detects Microstructural Changes in a Methamphetamine-Induced Mouse Model of Parkinson’s Disease. Neurotox Res 36, 724–735 (2019). https://doi.org/10.1007/s12640-019-00068-0

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Keywords

  • Behaviour
  • Diffusion kurtosis imaging
  • Methamphetamine
  • Mice
  • MRI
  • Parkinson’s disease
  • Tract-based spatial statistics