NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression
Emerging evidence suggests that astrocyte loss is one of the most important pathological features in the hippocampus of patients with major depressive disorder (MDD) and depressive mice. Pyroptosis is a recently discovered form of programmed cell death depending on Caspase–gasdermin D (Casp-GSDMD),...
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| Format: | Article |
| Language: | English |
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American Society for Clinical investigation
2021-12-01
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| Series: | JCI Insight |
| Subjects: | |
| Online Access: | https://doi.org/10.1172/jci.insight.146852 |
| _version_ | 1828807672877547520 |
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| author | Shanshan Li Yiming Sun Mengmeng Song Yuting Song Yinquan Fang Qingyu Zhang Xueting Li Nanshan Song Jianhua Ding Ming Lu Gang Hu |
| author_facet | Shanshan Li Yiming Sun Mengmeng Song Yuting Song Yinquan Fang Qingyu Zhang Xueting Li Nanshan Song Jianhua Ding Ming Lu Gang Hu |
| author_sort | Shanshan Li |
| collection | DOAJ |
| description | Emerging evidence suggests that astrocyte loss is one of the most important pathological features in the hippocampus of patients with major depressive disorder (MDD) and depressive mice. Pyroptosis is a recently discovered form of programmed cell death depending on Caspase–gasdermin D (Casp-GSDMD), which is involved in multiple neuropsychiatric diseases. However, the involvement of pyroptosis in the onset of MDD and glial pathological injury remains obscure. Here, we observed that depressive mice showed astrocytic pyroptosis, which was responsible for astrocyte loss, and selective serotonin reuptake inhibitor (SSRI) treatment could attenuate the pyroptosis induced by the chronic mild stress (CMS) model. Genetic KO of GSDMD, Casp-1, and astrocytic NOD-like receptor protein 3 (NLRP3) inflammasome in mice alleviated depression-like behaviors and inhibited the pyroptosis-associated protein expression. In contrast, overexpression of astrocytic GSDMD–N-terminal domain (GSDMD-N) in the hippocampus could abolish the improvement of behavioral alterations in GSDMD-deficient mice. This work illustrates that targeting the NLRP3/Casp-1/GSDMD–mediated pyroptosis may provide potential therapeutic benefits to stress-related astrocyte loss in the pathogenesis of depression. |
| first_indexed | 2024-12-12T08:28:27Z |
| format | Article |
| id | doaj.art-35cc40e68d204e86848698bd662b95e7 |
| institution | Directory Open Access Journal |
| issn | 2379-3708 |
| language | English |
| last_indexed | 2024-12-12T08:28:27Z |
| publishDate | 2021-12-01 |
| publisher | American Society for Clinical investigation |
| record_format | Article |
| series | JCI Insight |
| spelling | doaj.art-35cc40e68d204e86848698bd662b95e72022-12-22T00:31:10ZengAmerican Society for Clinical investigationJCI Insight2379-37082021-12-01623NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depressionShanshan LiYiming SunMengmeng SongYuting SongYinquan FangQingyu ZhangXueting LiNanshan SongJianhua DingMing LuGang HuEmerging evidence suggests that astrocyte loss is one of the most important pathological features in the hippocampus of patients with major depressive disorder (MDD) and depressive mice. Pyroptosis is a recently discovered form of programmed cell death depending on Caspase–gasdermin D (Casp-GSDMD), which is involved in multiple neuropsychiatric diseases. However, the involvement of pyroptosis in the onset of MDD and glial pathological injury remains obscure. Here, we observed that depressive mice showed astrocytic pyroptosis, which was responsible for astrocyte loss, and selective serotonin reuptake inhibitor (SSRI) treatment could attenuate the pyroptosis induced by the chronic mild stress (CMS) model. Genetic KO of GSDMD, Casp-1, and astrocytic NOD-like receptor protein 3 (NLRP3) inflammasome in mice alleviated depression-like behaviors and inhibited the pyroptosis-associated protein expression. In contrast, overexpression of astrocytic GSDMD–N-terminal domain (GSDMD-N) in the hippocampus could abolish the improvement of behavioral alterations in GSDMD-deficient mice. This work illustrates that targeting the NLRP3/Casp-1/GSDMD–mediated pyroptosis may provide potential therapeutic benefits to stress-related astrocyte loss in the pathogenesis of depression.https://doi.org/10.1172/jci.insight.146852Inflammation |
| spellingShingle | Shanshan Li Yiming Sun Mengmeng Song Yuting Song Yinquan Fang Qingyu Zhang Xueting Li Nanshan Song Jianhua Ding Ming Lu Gang Hu NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression JCI Insight Inflammation |
| title | NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression |
| title_full | NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression |
| title_fullStr | NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression |
| title_full_unstemmed | NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression |
| title_short | NLRP3/caspase-1/GSDMD–mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression |
| title_sort | nlrp3 caspase 1 gsdmd mediated pyroptosis exerts a crucial role in astrocyte pathological injury in mouse model of depression |
| topic | Inflammation |
| url | https://doi.org/10.1172/jci.insight.146852 |
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