Acrylamide exposure promotes the progression of depression-like behavior in mice with CUMS via GSDMD-mediated pyroptosis
AIM: We investigated the mechanism by which the environmental toxin acrylamide (AM) promotes depression. Methods: A depression mouse model was constructed using the chronic unpredictable mild stress method, AM was administered orally to simulate the exposure state. Depressive-like behavioral changes...
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Elsevier
2025-01-01
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| Series: | Ecotoxicology and Environmental Safety |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0147651324015197 |
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| author | JianFeng Liu Chenyang Han Jian Shen Yingcong Lin Heping Shen Genghuan Wang |
| author_facet | JianFeng Liu Chenyang Han Jian Shen Yingcong Lin Heping Shen Genghuan Wang |
| author_sort | JianFeng Liu |
| collection | DOAJ |
| description | AIM: We investigated the mechanism by which the environmental toxin acrylamide (AM) promotes depression. Methods: A depression mouse model was constructed using the chronic unpredictable mild stress method, AM was administered orally to simulate the exposure state. Depressive-like behavioral changes were assessed by open field test, elevated plus maze test, swimming test, and sucrose preference test. Enzyme-linked immunosorbent assay (ELISA) was used to detect tissue inflammatory factor levels, hematoxylin and eosin (H&E) and Nissl staining to detect neuronal damage, immunohistochemical staining to detect IBA-1 expression, and Western-blotting to detect protein levels. GSDMD knockout (KO) mice and the GSDMD inhibitor LDC7559 were used to inhibit GSDMD. In vitro, primary microglia were used, and AM intervention was applied to detect the levels of cellular inflammatory factors, and fluorescence staining was used to detect GSDMD-NT, and propidium iodide (PI) was used to detect the level of pyroptosis. Results: AM can exacerbate CUMS-like depression in mice, increase the levels of inflammatory factors in brain tissue, and worsen neuronal damage, with upregulation of IBA-1 expression, and can increase the expression of NLRP3, GSDMD, and GSDMD-NT. When GSDMD-KO or LDC7559 intervention was applied, it could antagonize the effects of AM and improve CUMS-like depression. In microglial cell experiments, AM could promote pyroptosis in microglial cells, increase the expression of inflammatory factors, and when GSDMD-KO was applied, it could inhibit the effects of AM. Conclusion: AM can promote the progression of depression in CUMS-like mice via GSDMD-mediated pyroptosis, while also increasing tissue inflammatory levels. GSDMD is an important target for the neurotoxicity of AM. |
| format | Article |
| id | doaj-art-615441520a3e499c9c40337909b6fbf2 |
| institution | Kabale University |
| issn | 0147-6513 |
| language | English |
| publishDate | 2025-01-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Ecotoxicology and Environmental Safety |
| spelling | doaj-art-615441520a3e499c9c40337909b6fbf22025-01-23T05:25:33ZengElsevierEcotoxicology and Environmental Safety0147-65132025-01-01289117443Acrylamide exposure promotes the progression of depression-like behavior in mice with CUMS via GSDMD-mediated pyroptosisJianFeng Liu0Chenyang Han1Jian Shen2Yingcong Lin3Heping Shen4Genghuan Wang5Department of Psychiatry, Xi’an Mental Health Center, Xi’an 710100, ChinaDepartment of neurosurgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, ChinaDepartment of neurosurgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, ChinaDepartment of neurosurgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, ChinaDepartment of neurosurgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, China; Corresponding authors.Department of neurosurgery, The Second Affiliated Hospital of Jiaxing University, Jiaxing 314001, China; Corresponding authors.AIM: We investigated the mechanism by which the environmental toxin acrylamide (AM) promotes depression. Methods: A depression mouse model was constructed using the chronic unpredictable mild stress method, AM was administered orally to simulate the exposure state. Depressive-like behavioral changes were assessed by open field test, elevated plus maze test, swimming test, and sucrose preference test. Enzyme-linked immunosorbent assay (ELISA) was used to detect tissue inflammatory factor levels, hematoxylin and eosin (H&E) and Nissl staining to detect neuronal damage, immunohistochemical staining to detect IBA-1 expression, and Western-blotting to detect protein levels. GSDMD knockout (KO) mice and the GSDMD inhibitor LDC7559 were used to inhibit GSDMD. In vitro, primary microglia were used, and AM intervention was applied to detect the levels of cellular inflammatory factors, and fluorescence staining was used to detect GSDMD-NT, and propidium iodide (PI) was used to detect the level of pyroptosis. Results: AM can exacerbate CUMS-like depression in mice, increase the levels of inflammatory factors in brain tissue, and worsen neuronal damage, with upregulation of IBA-1 expression, and can increase the expression of NLRP3, GSDMD, and GSDMD-NT. When GSDMD-KO or LDC7559 intervention was applied, it could antagonize the effects of AM and improve CUMS-like depression. In microglial cell experiments, AM could promote pyroptosis in microglial cells, increase the expression of inflammatory factors, and when GSDMD-KO was applied, it could inhibit the effects of AM. Conclusion: AM can promote the progression of depression in CUMS-like mice via GSDMD-mediated pyroptosis, while also increasing tissue inflammatory levels. GSDMD is an important target for the neurotoxicity of AM.http://www.sciencedirect.com/science/article/pii/S0147651324015197AcrylamideCUMSGSDMDPyroptosisInflammation |
| spellingShingle | JianFeng Liu Chenyang Han Jian Shen Yingcong Lin Heping Shen Genghuan Wang Acrylamide exposure promotes the progression of depression-like behavior in mice with CUMS via GSDMD-mediated pyroptosis Ecotoxicology and Environmental Safety Acrylamide CUMS GSDMD Pyroptosis Inflammation |
| title | Acrylamide exposure promotes the progression of depression-like behavior in mice with CUMS via GSDMD-mediated pyroptosis |
| title_full | Acrylamide exposure promotes the progression of depression-like behavior in mice with CUMS via GSDMD-mediated pyroptosis |
| title_fullStr | Acrylamide exposure promotes the progression of depression-like behavior in mice with CUMS via GSDMD-mediated pyroptosis |
| title_full_unstemmed | Acrylamide exposure promotes the progression of depression-like behavior in mice with CUMS via GSDMD-mediated pyroptosis |
| title_short | Acrylamide exposure promotes the progression of depression-like behavior in mice with CUMS via GSDMD-mediated pyroptosis |
| title_sort | acrylamide exposure promotes the progression of depression like behavior in mice with cums via gsdmd mediated pyroptosis |
| topic | Acrylamide CUMS GSDMD Pyroptosis Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0147651324015197 |
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