Han Yongsheng, Dong Jianjian, Xu Chenchen, Rao Rao, Shu Shan, Li Guangda, Cheng Nan, Wu Yun, Yang Hongyi, Han Yongzhu, Zhong Kai
Hospital Affiliated to the Institute of Neurology Anhui University of TCM, Hefei, China.
High Magnetic Field Laboratory, Hefei Institutes of Physical Science, Chinese Academy of Sciences (CAS), Hefei, China.
Front Behav Neurosci. 2020 Apr 22;14:59. doi: 10.3389/fnbeh.2020.00059. eCollection 2020.
In the current study, we used 9.4-tesla magnetic resonance imaging (9.4T MRI) and inductively coupled plasma mass spectrometry (ICP-MS) to investigate the distribution of copper in the brain samples of a murine model of Wilson's disease (WD) following penicillamine (PCA) treatment. We also evaluated if the distribution of copper in the brain samples of mice was correlated with behavioral symptoms. Results from the behavioral experiments showed that 7 days of PCA treatment decreased the total distance traveled in the open field and the number of rearing and climbing instances among the toxic milk (TX) mice as compared with model group. We also observed that the open arm ratio in the elevated plus-maze (EPM) was reduced, escape latency in the Barnes maze test was increased, and avoidance in the open field was enhanced in TX mice following 14 days of PCA treatment as compared with those in untreated TX mice. We found that PCA treatment for 21-28 days improved the cognitive abilities, exploratory behavior, and movement behavior of TX mice. The PCA-treated mice also exhibited varying degrees of magnetic susceptibilities in the cortex, corpus striatum, hippocampus, and amygdaloid nucleus across the treatment period. Low copper concentrations were found in all of the analyzed brain regions of PCA-treated mice after 21-28 days as compared with the model group ( < 0.05). However, copper concentrations were increased in the primary motor cortex and cerebellum at 7 days post-PCA treatment as compared with those in the model group ( < 0.05). After 14 days of PCA treatment, the copper concentrations in the sensorimotor cortex, corpus striatum, hippocampus, and amygdaloid nucleus were higher than those detected without treatment. The results from a Pearson's correlation analysis revealed that there was a significant ( < 0.05) correlation between copper concentrations and magnetic susceptibility in all of the brain regions that were analyzed. Therefore, our results indicate that copper concentration and magnetic susceptibility are associated with alterations in mood-related behavior, recognition memory, and movement behaviors in TX mice that are treated with PCA. The redistribution of copper in the TX mouse brain during PCA treatment may aggravate changes in behavioral performance.
在本研究中，我们使用9.4特斯拉磁共振成像（9.4T MRI）和电感耦合等离子体质谱法（ICP-MS）来研究青霉胺（PCA）治疗后威尔逊病（WD）小鼠模型脑样本中铜的分布情况。我们还评估了小鼠脑样本中铜的分布是否与行为症状相关。行为实验结果表明，与模型组相比，PCA治疗7天可减少毒性牛奶（TX）小鼠在旷场中的总行进距离以及直立和攀爬次数。我们还观察到，与未治疗的TX小鼠相比，PCA治疗14天后，TX小鼠在高架十字迷宫（EPM）中的开放臂比例降低，在巴恩斯迷宫试验中的逃避潜伏期增加，在旷场中的回避行为增强。我们发现，PCA治疗21 - 28天可改善TX小鼠的认知能力、探索行为和运动行为。在整个治疗期间，经PCA治疗的小鼠在皮质、纹状体、海马体和杏仁核中也表现出不同程度的磁化率。与模型组相比，21 - 28天后经PCA治疗的小鼠所有分析脑区中的铜浓度均较低（<0.05）。然而，与模型组相比，PCA治疗7天后初级运动皮质和小脑中的铜浓度升高（<0.05）。PCA治疗14天后，感觉运动皮质、纹状体、海马体和杏仁核中的铜浓度高于未治疗时检测到的浓度。皮尔逊相关分析结果显示，在所有分析的脑区中，铜浓度与磁化率之间存在显著相关性（<0.05）。因此，我们的结果表明，铜浓度和磁化率与经PCA治疗的TX小鼠的情绪相关行为、识别记忆和运动行为的改变有关。PCA治疗期间TX小鼠脑中铜的重新分布可能会加剧行为表现的变化。
