七氟醚麻醉诱导新生大鼠认知功能障碍的LncRNA GAS5调控机制

IF 1.4 4区医学 Q4 CLINICAL NEUROLOGY

Brain & Development Pub Date : 2024-11-16 DOI:10.1016/j.braindev.2024.10.003

Xi Chen, Yu Zhang, Nan Hu, Qian Pan, Kaiyuan Wang, Yiqing Yin

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引用次数: 0

摘要

背景和目的：七氟烷（Sev）暴露可能会对认知功能产生有害影响。本研究探讨了长非编码 RNA 生长停滞特异性转录本 5（LncRNA GAS5）在 Sev 诱导新生大鼠认知功能障碍中的作用机制：方法：用Sev麻醉7日龄Sprague-Dawley大鼠，诱导其认知功能障碍，然后用开阔地试验、新物体识别、径向臂迷宫和Morris水迷宫评估大鼠的认知功能。核细胞质分离实验检测了LncRNA GAS5的亚细胞定位，RNA pull down和双荧光素酶报告实验分别检测了miR-137与LncRNA GAS5和NKCC1的结合。向Sev大鼠海马注射腺病毒包装的sh-LncRNA GAS5，通过qRT-PCR和Western blot检测LncRNA GAS5、miR-137和NKCC1在大鼠海马中的表达：结果：Sev麻醉导致新生大鼠认知功能障碍。LncRNA GAS5在Sev大鼠中高表达，抑制LncRNA GAS5可缓解Sev诱导的大鼠认知功能障碍。LncRNA GAS5靶向miR-137，而miR-137抑制NKCC1的表达。敲除miR-137或过表达NKCC1可逆转抑制LncRNA GAS5对sev大鼠认知功能障碍的影响：结论：LncRNA GAS5通过miR-137/NKCC1轴促进Sev诱导的新生大鼠认知功能障碍。

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Regulatory mechanism of LncRNA GAS5 in cognitive dysfunction induced by sevoflurane anesthesia in neonatal rats

Background and objectives

Sevoflurane (Sev) exposure may provoke deleterious effects on cognitive function. This study explores the mechanism of long non-coding RNA growth arrest specific transcript 5 (LncRNA GAS5) in Sev-induced cognitive dysfunction in neonatal rats.

Methods

Cognitive dysfunction was induced by Sev anesthesia in 7-day-old Sprague-Dawley rats, followed by open field test, novel object recognition, radial arm maze, and Morris water maze to evaluate cognitive function of rats. The subcellular localization of LncRNA GAS5 was detected by nucleocytoplasmic isolation assay, and the binding of miR-137 to LncRNA GAS5 and NKCC1 was detected by RNA pull down and dual-luciferase reporter assay, respectively. Adenovirus-packaged sh-LncRNA GAS5 was injected into the hippocampus of Sev rats. qRT-PCR and Western blot were performed to detect the expressions of LncRNA GAS5, miR-137 and NKCC1 in the hippocampus of rats.

Results

Sev anesthesia led to cognitive dysfunction in neonatal rats. LncRNA GAS5 was highly expressed in Sev rats, and inhibition of LncRNA GAS5 alleviated Sev-induced cognitive dysfunction in rats. LncRNA GAS5 targeted miR-137, and miR-137 inhibited NKCC1 expression. Knockdown of miR-137 or overexpression of NKCC1 reversed the effect of LncRNA GAS5 inhibition on cognitive dysfunction in sev rats.

Conclusion

LncRNA GAS5 promotes Sev-induced cognitive dysfunction in neonatal rats via the miR-137/NKCC1 axis.

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来源期刊

Brain & Development 医学-临床神经学

CiteScore

3.60

自引率

0.00%

发文量

153

审稿时长

50 days

期刊介绍： Brain and Development (ISSN 0387-7604) is the Official Journal of the Japanese Society of Child Neurology, and is aimed to promote clinical child neurology and developmental neuroscience. The journal is devoted to publishing Review Articles, Full Length Original Papers, Case Reports and Letters to the Editor in the field of Child Neurology and related sciences. Proceedings of meetings, and professional announcements will be published at the Editor''s discretion. Letters concerning articles published in Brain and Development and other relevant issues are also welcome.