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Objective <p>This paper aimed to probe the role of the <i>LINC00641/miR-323a-3p/</i>EIF4G2 axis in regulating behavioral and brain monoamine neurotransmitter levels in a mouse model of depression induced by chronic unpredictable mild stress (CUMS).</p> Methods <p>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 <i>LINC00641, miR-323a-3p,</i> 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 <i>LINC00641, miR-323a-3p</i>, and EIF4G2 was validated experimentally.</p> Results <p>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 <i>LINC00641</i> or knockdown of <i>miR-323a-3p</i> significantly alleviated depression-like behaviors and restored monoamine neurotransmitter levels. LINC00641 regulated EIF4G2 expression by targeting <i>miR-323a-3p</i>, while <i>miR-323a-3p</i> and EIF4G2 also modulated depression through <i>LINC00641</i>.</p> Conclusion <p>Upregulation of <i>LINC00641</i> improves depression-like behaviors and enhances monoamine neurotransmission in CUMS mice via the <i>miR-323a-3p</i>/EIF4G2 axis, underscoring its potent as a therapeutic target for depression.</p> Graphical Abstract <p></p>

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

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年4月28日

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  • Ziqiao Lin,
  • Dong Qi,
  • Yongbo Zhang

摘要

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.

Graphical Abstract