Behavioural and histological changes in cuprizone-fed mice
Behavioural and histological changes in cuprizone-fed mice
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DOI：
10.1016/j.bbi.2020.01.021
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发表时间：
2020-07-01
影响因子：
15.1
通讯作者：
Shortland, Peter J.
中科院分区：
文献类型：
--
作者：
Sen, Monokesh K.;Almuslehi, Mohammed S. M.;Shortland, Peter J.
给小鼠喂食cuprizone（CPZ）会导致中枢神经系统（CNS）的脱髓鞘和反应性神经胶质增生，这是一些神经退行性疾病（如多发性硬化症）的标志。然而，关于与喂食CPZ相关的行为缺陷知之甚少，而且所知的大部分是相互矛盾的。本研究调查了37天口服0.2%CPZ的年轻成年小鼠诱发感觉运动行为的变化。行为测试包括伤害性退缩反射反应的测量和运动测试。此外，通过分析神经元和神经胶质细胞成分，将这些与相关CNS区域的组织学分析进行比较。与对照组相比，喂食CPZ的小鼠在梯子和横梁试验中表现出更多的脚滑。相比之下，各组之间对热或机械刺激的伤害性阈值没有变化。组织学分析显示整个CNS的脱髓鞘，这在大脑中的白色物质束中最突出，但在海马、基底神经节和间脑等区域也升高。在小脑深部核团和脑干前庭系统相关区域可见严重的脱髓鞘和胶质增生。然而，在脊髓中的变化很小。少突胶质细胞、神经元或运动神经元没有损失，但整个脊髓白色物质的星形胶质细胞染色显着增加。结果表明，CPZ差异影响整个中枢神经系统的少突胶质细胞，并诱导微妙的运动变化，如共济失调。这与运动和平衡功能相关的CNS区域（如小脑和脑干）的缺陷有关。
Feeding cuprizone (CPZ) to mice causes demyelination and reactive gliosis in the central nervous system (CNS), hallmarks of some neurodegenerative diseases like multiple sclerosis. However, relatively little is known regarding the behavioural deficits associated with CPZ-feeding and much of what is known is contradictory. This study investigated whether 37 days oral feeding of 0.2% CPZ to young adult mice evoked sensorimotor behavioural changes. Behavioural tests included measurements of nociceptive withdrawal reflex responses and locomotor tests. Additionally, these were compared to histological analysis of the relevant CNS regions by analysis of neuronal and glial cell components. CPZ-fed mice exhibited more foot slips in walking ladder and beam tests compared to controls. In contrast, no changes in nociceptive thresholds to thermal or mechanical stimuli occurred between groups. Histological analysis showed demyelination throughout the CNS, which was most prominent in white matter tracts in the cerebrum but was also elevated in areas such as the hippocampus, basal ganglia and diencephalon. Profound demyelination and gliosis was seen in the deep cerebellar nuclei and brain stem regions associated with the vestibular system. However, in the spinal cord changes were minimal. No loss of oligodendrocytes, neurons or motoneurons occurred but a significant increase in astrocyte staining ensued throughout the white matter of the spinal cord. The results suggest that CPZ differentially affects oligodendrocytes throughout the CNS and induces subtle motor changes such as ataxia. This is associated with deficits in CNS regions associated with motor and balance functions such as the cerebellum and brain stem.