Behavioural alterations and morphological changes are attenuated by the lack of TRPA1 receptors in the cuprizone-induced demyelination model in mice
Behavioural alterations and morphological changes are attenuated by the lack of TRPA1 receptors in the cuprizone-induced demyelination model in mice
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DOI：
10.1016/j.jneuroim.2018.03.020
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发表时间：
2018-07-15
影响因子：
3.3
通讯作者：
Pinter, Erika
中科院分区：
文献类型：
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作者：
Bolcskei, Kata;Kriszta, Gabor;Pinter, Erika
我们最近报道，瞬时受体电位锚蛋白1（TRPA1）受体缺陷显着衰减铜腙诱导的脱髓鞘通过减少成熟少突胶质细胞的凋亡。本研究的目的是收集更多的数据，TRPA1的作用，通过调查的时间过程中的行为改变和形态学变化的cuprizone处理的TRPA1受体基因deficiencymice.Demyelination诱导喂养雄性野生型（WT）和TRPA1基因缺失（TRPA1 KO）小鼠与0.2%的cuprizone 6周。每周进行一次行为测试，以跟踪cuprizone诱导的功能变化。机械伤害性阈值的动态足底感觉计和冯弗雷细丝进行了研究。通过加速RotaRod和水平网格测试评估电机性能。对于自发活动的研究，使用了旷场试验。胼胝体脱髓鞘的时间进程也通过磁共振成像（MRI）每周进行一次。在第3周用Luxol Fast Blue（LFB）染色和在第6周用电子显微镜（EM）进行髓鞘丢失的组织学分析。通过免疫组织化学（IHC）评估第3周星形胶质细胞和小胶质细胞的积聚。在开放的竞技场中，铜腙处理的小鼠花费更多的时间与运动，他们的平均速度显着更高，他们旅行的距离比未处理的小鼠更长。WT和TRPA1 KO小鼠在这些参数中未检测到统计学差异。另一方面，与TRPA1 KO动物相比，WT小鼠中诱导了显著增加的直立行为。MRI，LFB，IHC和EM分析检测到的形态学变化显示，减少损伤的髓鞘和衰减的积累的星形胶质细胞和小胶质细胞在cuprizone处理的TRPA1基因敲除动物，在每个检查的时间点，我们最近的数据进一步表明，抑制TRPA1受体可能是一个有前途的治疗方法，以限制中枢神经系统损伤的脱髓鞘疾病。
We have recently reported that the Transient Receptor Potential Ankyrin 1 (TRPA1) receptor deficiency significantly attenuated cuprizone-induced demyelination by reducing the apoptosis of mature oligodendrocytes. The aim of the present study was to gather additional data on the role of TRPA1 by investigating the time course of behavioural alterations and morphological changes in cuprizone-treated TRPA1 receptor gene-deficient mice.Demyelination was induced by feeding male wild-type (WT) and TRPA1 gene-deleted (TRPA1 KO) mice with 0.2% cuprizone for 6 weeks. Behavioural tests were performed once per week to follow cuprizone-induced functional changes. Mechanonociceptive thresholds were investigated by a dynamic plantar aesthesiometer and von Frey filaments. Motor performance was assessed by accelerating RotaRod and horizontal grid tests. For the study of spontaneous activity, the open field test was used. The time course of corpus callosum demyelination was also followed weekly by magnetic resonance imaging (MRI). Histological analysis of myelin loss was performed with Luxol Fast Blue (LFB) staining at week 3 and electron microscopy (EM) at week 6. Astrocyte and microglia accumulation at week 3 was assessed by immunohistochemistry (IHC).Cuprizone treatment induced no changes in mechanonociception or motor performance. In the open arena, cuprizone-treated mice spent more time with locomotion, their mean velocity was significantly higher and the distance they travelled was longer than untreated mice. No statistical difference was detected between WT and TRPA1 KO mice in these parameters. On the other hand, significantly increased rearing behaviour was induced in WT mice compared to TRPA1 KO animals. Morphological changes detected with MRI, LFB, IHC and EM analysis revealed reduced damage of the myelin and attenuated accumulation of astrocytes and microglia in cuprizone-treated TRPA1 KO animals, at each examined time point.Our recent data further suggest that inhibition of TRPA1 receptors could be a promising therapeutic approach to limit central nervous system damage in demyelinating diseases.