Nimodipine attenuates dibutyl phthalate‐induced learning and memory impairment in kun ming mice: An in vivo study based on bioinformatics analysis,Environmental Toxicology

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Nimodipine attenuates dibutyl phthalate‐induced learning and memory impairment in kun ming mice: An in vivo study based on bioinformatics analysis
Environmental Toxicology ( IF 4.4 ) Pub Date : 2020-12-18 , DOI: 10.1002/tox.23084
Biao Yan ₁ , Ping Ma ₁ , Shaohui Chen ₁ , Hongguo Cheng ₂ , Min Tang ₃ , Yanling Sun ₁ , Xu Yang ₁ , Yang Wu ₁ , Menglin Cheng ₁

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Dibutyl phthalate (DBP), a typical representative of phthalate esters (PAEs), is used as a plasticizer in various industrial applications and has been reported to be responsible for neurobehavioral changes. Despite mounting evidence showing that nimodipine (Nim) palys a neuropharmacological and psychopharmacological role in neurons, the attenuating effects of Nim on learning and memory impairment induced by DBP exposure remain unknown. Based on bioinformatics analysis we found that the biological processes affected by both DBP and Nim may involve the calcium signaling pathway, the MAPK signaling pathway and the apoptosis pathway. The results of an in vivo study confirmed that DBP affects the levels of Ca2+ -related proteins, up-regulates phosphorylated -ERK1/2 expression and results in hippocampal neuronal damage and apoptosis, whereas Nim as a Ca2+ antagonist, has a certain neuroprotective role to avoid these adverse effects. Our data suggest that Nim could be used to attenuate the learning and memory impairment in DBP-exposed mice, to down-regulate intracellular Ca2+ levels, subordinate the ERK1/2 pathway and attenuate apoptosis in hippocampal tissue.

中文翻译：

尼莫地平减轻昆明小鼠邻苯二甲酸二丁酯诱导的学习记忆障碍：基于生物信息学分析的体内研究

邻苯二甲酸二丁酯 (DBP) 是邻苯二甲酸酯 (PAE) 的典型代表，在各种工业应用中用作增塑剂，据报道它会导致神经行为变化。尽管越来越多的证据表明尼莫地平 (Nim) 在神经元中发挥神经药理学和精神药理学作用，但 Nim 对 DBP 暴露引起的学习和记忆障碍的减弱作用仍然未知。基于生物信息学分析，我们发现 DBP 和 Nim 共同影响的生物过程可能涉及钙信号通路、MAPK 信号通路和细胞凋亡通路。体内研究结果证实，DBP 影响 Ca2+ 相关蛋白的水平，上调磷酸化 -ERK1/2 表达并导致海马神经元损伤和细胞凋亡，而 Nim 作为 Ca2+ 拮抗剂，具有一定的神经保护作用，可以避免这些不良反应。我们的数据表明 Nim 可用于减轻 DBP 暴露小鼠的学习和记忆障碍，下调细胞内 Ca2+ 水平，从属 ERK1/2 通路并减弱海马组织的细胞凋亡。

更新日期：2020-12-18

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