长链非编码RNA GAS5在新生大鼠七氟醚麻醉诱导的认知功能障碍中的调控机制

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

作者信息

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

机构信息

Department of Anesthesiology, Tianjin Medical University Cancer Institute and Hospital, National Clinical Research Center for Cancer, Key Laboratory of Cancer Prevention and Therapy, Tianjin, Tianjin 's Clinical Research Center for Cancer, Tianjin 300060, China.

出版信息

Brain Dev. 2025 Feb;47(1):104295. doi: 10.1016/j.braindev.2024.10.003. Epub 2024 Nov 16.

DOI:10.1016/j.braindev.2024.10.003

PMID:39550980

Abstract

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.

摘要

背景与目的

七氟醚（Sev）暴露可能对认知功能产生有害影响。本研究探讨长链非编码RNA生长停滞特异性转录本5（LncRNA GAS5）在新生大鼠七氟醚诱导的认知功能障碍中的作用机制。

方法

对7日龄的Sprague-Dawley大鼠进行七氟醚麻醉以诱导认知功能障碍，随后进行旷场试验、新物体识别试验、放射状臂迷宫试验和Morris水迷宫试验以评估大鼠的认知功能。通过核质分离试验检测LncRNA GAS5的亚细胞定位，分别通过RNA下拉试验和双荧光素酶报告基因试验检测miR-137与LncRNA GAS5和NKCC1的结合情况。将腺病毒包装的sh-LncRNA GAS5注射到七氟醚处理大鼠的海马体中。采用qRT-PCR和蛋白质免疫印迹法检测大鼠海马体中LncRNA GAS5、miR-137和NKCC1的表达。

结果

七氟醚麻醉导致新生大鼠出现认知功能障碍。LncRNA GAS5在七氟醚处理的大鼠中高表达，抑制LncRNA GAS5可减轻七氟醚诱导的大鼠认知功能障碍。LncRNA GAS5靶向miR-137，miR-137抑制NKCC1的表达。敲低miR-137或过表达NKCC1可逆转LncRNA GAS5抑制对七氟醚处理大鼠认知功能障碍的影响。