ALOX15B-GPX4 Axis in Alleviates Depression by Regulating Neuroinflammation and Ferroptosis

Shu’e ZENG; Zhixing LU; Yanjun WANG; Tian MENG; Ruina LIU

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Shu’e ZENG, Zhixing LU, Yanjun WANG, Tian MENG, Ruina LIU. ALOX15B-GPX4 Axis in Alleviates Depression by Regulating Neuroinflammation and Ferroptosis[J]. Journal of Kunming Medical University.

Citation:

Shu’e ZENG, Zhixing LU, Yanjun WANG, Tian MENG, Ruina LIU. ALOX15B-GPX4 Axis in Alleviates Depression by Regulating Neuroinflammation and Ferroptosis[J]. Journal of Kunming Medical University.

Shu’e ZENG, Zhixing LU, Yanjun WANG, Tian MENG, Ruina LIU. ALOX15B-GPX4 Axis in Alleviates Depression by Regulating Neuroinflammation and Ferroptosis[J]. Journal of Kunming Medical University.

Citation:

Shu’e ZENG, Zhixing LU, Yanjun WANG, Tian MENG, Ruina LIU. ALOX15B-GPX4 Axis in Alleviates Depression by Regulating Neuroinflammation and Ferroptosis[J]. Journal of Kunming Medical University.

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ALOX15B-GPX4 Axis in Alleviates Depression by Regulating Neuroinflammation and Ferroptosis

1.
Department of Geriatrics，Yunnan Provincial Mental Health Hospital，Kunming Yunnan 650224
2.
Department of Research and Development Center，Yunnan Yunke Institute of Biotechnology，Yunnan Kunming 650500
3.
Department of Clinical Skills Center，Yunnan Provincial Mental Health Hospital，Kunming Yunnan 650224
4.
Department of Project Management，Yunnan Yunke Institute of Biotechnology，Yunnan Kunming 650500，China

Received Date: 2025-12-14

Abstract

Abstract

Objective To investigate the role of arachidonate 15-lipoxygenase type B （ALOX15B） in depression and its potential molecular mechanisms. Methods A chronic unpredictable mild stress （CUMS） depression model was established in rats. Sucrose preference test, forced swimming test, and tail suspension test were used to detect depressive-like behaviors in rats. An in vitro cell model was established by treating BV2 cells with lipopolysaccharide （LPS）. Cell viability was assessed using the CCK-8 assay, and cell apoptosis was detected by flow cytometry. The levels of inflammatory cytokines in tissues and cells were measured using ELISA kits. The contents of Fe²⁺, malondialdehyde （MDA）, glutathione （GSH）, and superoxide dismutase （SOD） in tissues and cells were determined using biochemical assay kits. The expression levels of ALOX15B, GPX4, ACSL4, TFR1, FIH1, and SLC7A11 in tissues and cells were detected by RT-qPCR and Western blot. Immunofluorescence staining was performed to detect the expression of ionized calcium-binding adaptor molecule 1 （IBA-1） in cells. Results ALOX15B was significantly upregulated in both the CUMS rat model and the LPS-induced BV2 cell model （P < 0.0001）, whereas GPX4 was significantly downregulated （P < 0.0001）. Knockdown of ALOX15B alleviated depression-like behaviors in rats. In the hippocampal tissues of rats with ALOX15B knockdown, the levels of Fe²⁺ and MDA were significantly decreased （P < 0.0001）, while the levels of SOD and GSH were significantly increased （P < 0.0001）. ACSL4 and TFR1 protein expression were significantly decreased （P < 0.01）, whereas FIH1 and SLC7A11 protein expression were significantly increased （P < 0.001）. ALOX15B knockdown significantly alleviated LPS-induced decreases in cell viability and increases in cell apoptosis rate. In addition, Fe²⁺ and MDA levels were significantly reduced in ALOX15B-knockdown cells （P < 0.01）, while GSH and SOD levels were increased （P < 0.01）. ACSL4 and TFR1 protein expression were significantly decreased （P < 0.01）, whereas FIH1 and SLC7A11 protein expression were significantly increased （P < 0.001）. Co-immunoprecipitation assays confirmed an interaction between ALOX15B and GPX4, and GPX4 knockdown reversed the cytoprotective effects mediated by ALOX15B silencing. Conclusion ALOX15B knockdown alleviates the progression of depression by attenuating neuroinflammation and inhibiting ferroptosis.
- Ferroptosis,
- Neuroinflammation,
- ALOX15B,
- Depression

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References(29)

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