CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy

CXCR4 antagonist AMD3100 reverses the neurogenesis promoted by enriched environment and suppresses long-term seizure activity in adult rats of temporal lobe epilepsy
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CXCR4拮抗剂AMD3100逆转丰富环境促进的神经发生并抑制成年颞叶癫痫大鼠的长期癫痫发作活动

DOI:
10.1016/j.bbr.2017.01.014
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发表时间:
2017-03
影响因子:
2.7
通讯作者:
Zhao Chuansheng
Zhao Chuansheng
中科院分区:
心理学3区
文献类型:
--
作者:
Zhou Zhike;Liu Tingting;Sun Xiaoyu;Mu Xiaopeng;Zhu Gang;Xiao Ting;Zhao Mei;Zhao Chuansheng

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丰富环境(EE)可促进成年颞叶癫痫(TLE)大鼠海马神经发生,改善认知功能障碍,并伴有基质细胞衍生因子-1(SDF-1)表达增加。我们研究了癫痫发作后EE诱导的神经发生增强和认知功能改善是否由SDF-1/CXCR 4通路介导。因此,我们研究了EE联合CXCR 4拮抗剂AMD 3100对TLE模型中神经发生、认知功能和长期癫痫活动的影响。成年大鼠随机分为对照组、EE组、SE组、SE后EE组、AMD 3100组和EE + AMD 3100组。免疫荧光染色观察海马神经发生情况,尼氏染色观察海马损伤情况。脑电图用于测量自发性癫痫发作的频率和平均持续时间。采用Morris水迷宫测试评价认知功能。EE治疗显著改善了认知功能障碍,降低了长期发作活动,这些作用可能通过SDF-1/CXCR 4通路在TLE慢性期介导。虽然AMD 3100逆转了EE对神经发生的影响,但它并没有消除癫痫发作后EE诱导的认知改善。更重要的是,EE联合AMD 3100治疗显著抑制了长期癫痫发作活动,这为治疗TLE提供了有希望的证据。
It has been showed that enriched environment (EE) enhances the hippocampal neurogenesis and improves the cognitive impairments, accompanied by the increased expressions of stromal cell-derived factor-1 (SDF-1) in adult rats of temporal lobe epilepsy (TLE). We examined whether the enhanced neurogenesis and improved cognitive functions induced by EE following seizures were mediated by SDF-1/CXCR4 pathway. Therefore, we investigated the effects of the EE combined with CXCR4 antagonist AMD3100 on neurogenesis, cognitive functions and the long-term seizure activity in the TLE model. Adult rats were randomly assigned as control rats, rats treated with EE, rats subjected to status epilepticus (SE), post-SE rats treated with EE, AMD3100 or EE combined with AMD3100 respectively. We used immunofluorescence staining to analyze the hippocampal neurogenesis and Nissl staining to evaluate hippocampal damage. Electroencephalography was used to measure the frequency and mean duration of spontaneous seizures. Cognitive function was evaluated by Morris water maze test. EE treatment significantly, as well as improved cognitive impairments and decreased long-term seizure activity, and that these effects might be mediated through SDF-1/CXCR4 pathway during the chronic stage of TLE. Although AMD3100 reversed the effect of EE on neurogenesis, it did not abolish the cognitive improvement induced by EE following seizures. More importantly, EE combined with AMD3100 treatment significantly suppressed long-term seizure activity, which provided promising evidences to treat TLE.
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