Diffusion Kurtosis Imaging Detects Microstructural Changes in a Methamphetamine-Induced Mouse Model of Parkinson's Disease
Diffusion Kurtosis Imaging Detects Microstructural Changes in a Methamphetamine-Induced Mouse Model of Parkinson's Disease
复制标题
DOI：
10.1007/s12640-019-00068-0
复制
发表时间：
2019-11-01
影响因子：
3.7
通讯作者：
Khairnar, Amit
中科院分区：
文献类型：
--
作者：
Arab, Anas;Ruda-Kucerova, Jana;Khairnar, Amit
众所周知，滥用甲基苯丙胺(METH)会增加患帕金森病(PD)的风险，这是因为它具有多巴胺能神经毒性。这就是通过中毒冰毒剂量(10 mg/kg，每2小时四次)建立帕金森病模型的基本原理，该模型的特征是强烈的神经退行性变和典型的小鼠运动障碍。在这项研究中，我们使用扩散峰度成像来揭示冰毒诱导的神经变性引起的脑微结构变化。用Bruker Avance 9.4Tesla磁共振成像系统在5天和1个月两个时间点对冰毒处理的小鼠和生理盐水对照组进行扩散峰度成像扫描，以捕捉冰毒引起的早期和晚期变化。5天后，我们发现黑质、纹状体和感觉运动皮质的峰度减少，这可能表明DAR能神经元的丢失。1个月时，纹状体、感觉运动皮质和海马区峰度增加，可能反映了一定的恢复过程。此外，我们对白质进行了基于束的空间统计分析，在1个月时，我们观察到外侧丘脑腹侧核和部分丘脑外侧核的峰度增加。在早期阶段没有任何变化。这项研究证实了弥散峰度成像能够检测帕金森病模型中灰质和白质的微结构病理过程。峰度变化的确切机制尚不清楚，但峰度变化似乎是追踪帕金森病和其他神经退行性疾病脑微结构变化的一个有价值的生物标志物。
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.