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Deep rTMS Mitigates Behavioral and Neuropathologic Anomalies in Cuprizone-Exposed Mice Through Reducing Microglial Proinflammatory Cytokines
Frontiers in Integrative Neuroscience ( IF 2.6 ) Pub Date : 2020-10-05 , DOI: 10.3389/fnint.2020.556839
Liu Yang , Yawen Su , Fannv Guo , Handi Zhang , Yinglin Zhao , Qinjun Huang , Haiyun Xu

In comparison to conventional repetitive transcranial magnetic stimulation (rTMS), theta burst stimulation is stronger and more effective as a brain stimulation approach within short periods. Although this deep rTMS technique is being applied in treating neuropsychiatric disorders, few animal studies have attempted to clarify the neurobiological mechanisms underlying its beneficial effects. This animal study examined the effects of deep rTMS on the cuprizone-induced neuropathologic and behavioral anomalies and explored the underlying mechanism. Adolescent male C57BL/6 mice were fed a rodent chow without or with cuprizone (CPZ; 0.2% w/w) for 5 weeks. Another two groups of mice were subjected to deep rTMS or sham rTMS once a day during weeks 2–5 of the CPZ-feeding period. The behaviors of all mice were assessed after the withdrawal of CPZ before neuropathological and immunological analyses. Compared to the CNT group, mice in CPZ and CPZ + Sham groups showed deficits in social recognition and spatial working memory as well as anxiety-like behavior, in addition to myelin breakdown and OL loss in the corpus callosum (CC), caudate putamen, cerebral cortex, and hippocampus of the brain. Deep rTMS effectively reduced behavioral anomalies and blocked myelin breakdown and OL loss in CPZ-fed mice. Besides, it also dampened microglia activation at lesion sites and rectified cytokines levels (IL-1β, IL-6, and IL-10) in CPZ-affected regions. The most significant effect was seen in the cerebral cortex where alleviated neuropathology co-existed with less microglia activation and higher IL-10 level. These data provided experimental evidence for the beneficial effects of deep rTMS in CPZ-fed mice and revealed a neurobiological mechanism of the modality.



中文翻译:

Deep rTMS通过减少小胶质促炎细胞因子减轻了铜riz暴露小鼠的行为和神经病理异常。

与传统的重复经颅磁刺激(rTMS)相比,θ爆裂刺激在短期内作为大脑刺激方法更强大,更有效。尽管这种深层rTMS技术已用于治疗神经精神疾病,但很少有动物研究试图阐明其有益作用的神经生物学机制。这项动物研究检查了深rTMS对cuprizone诱导的神经病理和行为异常的影响,并探讨了其潜在机制。给青春期的雄性C57BL / 6小鼠喂食不含或不含铜酮(CPZ; 0.2%w / w)的啮齿动物饲料5周。在CPZ喂养期的第2-5周,每天对另外两组小鼠进行深rTMS或假rTMS。撤离CPZ后评估所有小鼠的行为,然后进行神经病理学和免疫学分析。与CNT组相比,CPZ和CPZ + Sham组的小鼠表现出社交识别和空间工作记忆以及焦虑样行为方面的缺陷,此外还有my体(CC),尾状壳状核中的髓磷脂降解和OL丢失,大脑皮层和大脑海马体。Deep rTMS有效减少了CPZ喂养小鼠的行为异常,并阻止了髓磷脂分解和OL丢失。此外,它还抑制了受CPZ影响区域的病变部位的小胶质细胞活化和纠正的细胞因子水平(IL-1β,IL-6和IL-10)。在大脑皮层中观察到最显着的效果,其中缓解的神经病理学与较少的小胶质细胞活化和较高的IL-10水平共存。

更新日期:2020-11-06
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