Effects of the LINC00641/miR-323a-3p/EIF4G2 axis on behaviors and brain monoamine neurotransmitters in chronic unpredictable mild stress mice.

IF 5.3 2区医学 Q2 CELL BIOLOGY

Cell Biology and Toxicology Pub Date : 2025-04-28 DOI:10.1007/s10565-025-10015-9

Ziqiao Lin, Dong Qi, Yongbo Zhang

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引用次数: 0

Abstract

Objective: This paper aimed to probe the role of the LINC00641/miR-323a-3p/EIF4G2 axis in regulating behavioral and brain monoamine neurotransmitter levels in a mouse model of depression induced by chronic unpredictable mild stress (CUMS).

Methods: A CUMS-induced depression model was established in mice. A series of behavioral tests, comprising the sucrose preference, tail suspension, as well as forced swimming tests, were conducted. Levels of LINC00641, miR-323a-3p, and EIF4G2 in hippocampal tissues were measured. Biochemical indices, including 5-HT, NE, and DA, were analyzed. Hippocampal neuron structure and apoptosis were evaluated. The targeting relationship among LINC00641, miR-323a-3p, and EIF4G2 was validated experimentally.

Results: CUMS mice exhibited reduced sucrose preference, prolonged immobilization time in behavioral tests, decreased 5-HT, NE, and DA levels, and increased hippocampal neuron apoptosis. Overexpression of LINC00641 or knockdown of miR-323a-3p significantly alleviated depression-like behaviors and restored monoamine neurotransmitter levels. LINC00641 regulated EIF4G2 expression by targeting miR-323a-3p, while miR-323a-3p and EIF4G2 also modulated depression through LINC00641.

Conclusion: Upregulation of LINC00641 improves depression-like behaviors and enhances monoamine neurotransmission in CUMS mice via the miR-323a-3p/EIF4G2 axis, underscoring its potent as a therapeutic target for depression.

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LINC00641/miR-323a-3p/EIF4G2轴对慢性不可预测轻度应激小鼠行为和脑单胺类神经递质的影响

目的：探讨LINC00641/miR-323a-3p/EIF4G2轴在慢性不可预测轻度应激（CUMS）抑郁症小鼠模型中调节行为和脑单胺类神经递质水平的作用。方法：建立cms诱导小鼠抑郁模型。进行了一系列的行为测试，包括蔗糖偏好测试、悬尾测试和强迫游泳测试。检测海马组织中LINC00641、miR-323a-3p和EIF4G2的水平。分析5-羟色胺、NE、DA等生化指标。观察海马神经元结构及凋亡情况。实验验证了LINC00641、miR-323a-3p和EIF4G2之间的靶向关系。结果：CUMS小鼠表现出糖偏好降低，行为测试中固定时间延长，5-羟色胺、NE和DA水平降低，海马神经元凋亡增加。过表达LINC00641或敲低miR-323a-3p可显著缓解抑郁样行为，恢复单胺类神经递质水平。LINC00641通过靶向miR-323a-3p调节EIF4G2的表达，而miR-323a-3p和EIF4G2也通过LINC00641调节抑郁症。结论：上调LINC00641可改善CUMS小鼠的抑郁样行为，并通过miR-323a-3p/EIF4G2轴增强单胺神经传递，强调其作为抑郁症治疗靶点的有效性。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Cell Biology and Toxicology 生物-毒理学

CiteScore

9.90

自引率

4.90%

发文量

101

审稿时长

>12 weeks

期刊介绍： Cell Biology and Toxicology (CBT) is an international journal focused on clinical and translational research with an emphasis on molecular and cell biology, genetic and epigenetic heterogeneity, drug discovery and development, and molecular pharmacology and toxicology. CBT has a disease-specific scope prioritizing publications on gene and protein-based regulation, intracellular signaling pathway dysfunction, cell type-specific function, and systems in biomedicine in drug discovery and development. CBT publishes original articles with outstanding, innovative and significant findings, important reviews on recent research advances and issues of high current interest, opinion articles of leading edge science, and rapid communication or reports, on molecular mechanisms and therapies in diseases.