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

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.