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.

• Klíčová slova
• Behaviour, Diffusion kurtosis imaging, MRI, Methamphetamine, Mice, Parkinson’s disease, Tract-based spatial statistics,
• MeSH
• chování zvířat účinky léků   MeSH
• difuzní magnetická rezonance MeSH
• dopaminové látky toxicita   MeSH
• methamfetamin toxicita   MeSH
• modely nemocí na zvířatech MeSH
• mozek diagnostické zobrazování   účinky léků   patologie   MeSH
• myši inbrední C57BL MeSH
• Parkinsonova nemoc sekundární diagnostické zobrazování   patologie   MeSH
• zvířata MeSH
• Check Tag
• mužské pohlaví MeSH
• zvířata MeSH
• Publikační typ
• časopisecké články MeSH
• Názvy látek
• dopaminové látky MeSH
• methamfetamin MeSH