Early-Life Multiple Sevoflurane Exposures Alleviate Long-term Anxiety-Like Behaviors in Mice via the proBDNF/ERK Pathway
Early-Life Multiple Sevoflurane Exposures Alleviate Long-term Anxiety-Like Behaviors in Mice via the proBDNF/ERK Pathway
复制标题
生命早期多次七氟烷暴露可通过 proBDNF/ERK 通路缓解小鼠的长期焦虑样行为
DOI：
10.1007/s12035-020-02113-y
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发表时间：
2020-09
影响因子：
5.1
通讯作者：
Dai Ru-Ping
中科院分区：
文献类型：
--
作者：
Luo Ru-Yi;Luo Cong;Zhong Feng;Shen Wei-Yun;Li Hui;Zhang Yan-Ling;Dai Ru-Ping
早期接触多种麻醉药会对发育中的大脑造成神经毒性和认知功能障碍。然而，早期生活中的多重七氟烷暴露对情绪变化的影响，特别是对压力的影响，远远超出了人们的理解。在C57BL6/J年轻雄性小鼠中，本研究发现连续3天吸入3%七氟醚2 h对开放性实验、明暗转换实验和升高加迷宫实验的焦虑样行为没有影响。此外，足部冲击应激诱导了短期和长期的焦虑样行为。然而，三倍七氟醚暴露改善了足部电击引起的长期焦虑样行为。与此同时，足部冲击应激上调了前扣带皮层（ACC）中磷酸化的细胞外信号调节激酶（p-ERK）和脑源性神经营养因子前体（proBDNF）的表达，而三氟醚暴露显著抑制了这两种表达。免疫荧光进一步显示p-ERK的增加主要表达在probdnf阳性染色细胞中。acc内注射重组proBDNF蛋白上调p-ERK表达，阻断七氟醚暴露对长期焦虑样行为的抗焦虑作用。因此，我们的研究表明，多次暴露于七氟醚可以通过抑制ACC中的proBDNF-ERK信号传导来缓解幼年小鼠急性应激时的长期焦虑样行为。
Early-life multiple anesthetics exposure causes neurotoxicity and hence cognitive dysfunction on developing brain. However, the effects of early-life multiple sevoflurane exposures on emotional changes, especially upon stress, are far beyond understood. In young male C57BL6/J mice, the present study showed that 3% sevoflurane inhalation for 2 h in three consecutive days did not influence anxiety-like behaviors as measured by open field test, light dark transition, and elevated plus maze test. In addition, foot shocks stress induced both the short- and long-term anxiety-like behaviors. However, triple sevoflurane exposures ameliorated the long-term anxiety-like behaviors induced by the foot shocks. In parallel, foot shocks stress upregulated the expression of phosphorylated extracellular signal-regulated kinase (p-ERK) and brain-derived neurotrophic factor precursor (proBDNF) in the anterior cingulate cortex (ACC), which were significantly inhibited by triple sevoflurane exposures. Immunofluorescence further indicated that the increased p-ERK was mainly expressed in the proBDNF-positive staining cells. Intra-ACC injection of recombinant proBDNF protein upregulated the p-ERK expression and blocked the anxiolytic effect of sevoflurane exposure on long-term anxiety-like behaviors. Therefore, our study demonstrated that multiple sevoflurane exposures alleviate long-term anxiety-like behaviors upon acute stress in young mice by inhibiting proBDNF-ERK signaling in the ACC.
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DOI：
10.18632/aging.101673
发表时间：
2018-12
期刊：
Aging (Albany NY)
影响因子：
--
作者：
Xin Zhao;Yanwu Jin;Haibo Li;Yuxiu Jia;Yuelan Wang
通讯作者：
Xin Zhao;Yanwu Jin;Haibo Li;Yuxiu Jia;Yuelan Wang
影响因子：
1.9
作者：
V. Lecompte;C. Rousseau
通讯作者：
V. Lecompte;C. Rousseau
外周脑源性神经营养因子前体作为炎症介质调节疼痛
影响因子：
4.6
作者：
Luo C;Zhong XL;Zhou FH;Li JY;Zhou P;Xu JM;Song B;Li CQ;Zhou XF;Dai RP
通讯作者：
Dai RP
影响因子：
7.6
作者：
J. Lynch;P. Winiecki;T. L. Gilman;Jordan M. Adkins;A. Jasnow
通讯作者：
J. Lynch;P. Winiecki;T. L. Gilman;Jordan M. Adkins;A. Jasnow
ProBDNF 在单核细胞功能中的调节作用：对斯坦福 A 型主动脉夹层疾病的影响
影响因子：
4.8
作者：
Shen, Wei-Yun;Luo, Cong;Dai, Ru-Ping
通讯作者：
Dai, Ru-Ping