Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice.
Background: Reports indicate that depression is a common mental health issue following traumatic brain injury (TBI). Our prior research suggests that Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-related neuroinflammation, modulated by glial cells such as astrocytes, is l...
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| Format: | Article |
| Language: | English |
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Elsevier
2025-02-01
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| Series: | Neurobiology of Disease |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0969996124003875 |
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| author | Hui-Tao Miao Jun Wang Jing-Jing Shao Rong-Xin Song Wen-Guang Li Jian-Kai Sun Shi-Yan Jia Dong-Xue Zhang Xiao-Ming Li Jian-Yong Zhao Li-Min Zhang |
| author_facet | Hui-Tao Miao Jun Wang Jing-Jing Shao Rong-Xin Song Wen-Guang Li Jian-Kai Sun Shi-Yan Jia Dong-Xue Zhang Xiao-Ming Li Jian-Yong Zhao Li-Min Zhang |
| author_sort | Hui-Tao Miao |
| collection | DOAJ |
| description | Background: Reports indicate that depression is a common mental health issue following traumatic brain injury (TBI). Our prior research suggests that Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-related neuroinflammation, modulated by glial cells such as astrocytes, is likely to play a crucial role in the progression of anxiety and cognitive dysfunction. However, there is limited understanding of the potential of astrocytic NLRP3 in treating depression under mild TBI condition. This study aimed to determine whether astrocytic NLRP3 knockout (KO) could mitigate depressive-like behaviors following mild TBI and explore potential variations in such behaviors between genders post-mild TBI. Methods: Mild TBI was induced in mice using Feeney's weight-drop method. Behavioral assessments included neurological severity scores (NSS), social interaction test (SI), tail suspension test (TST), and forced swimming test (FST). Pathological changes were evaluated through immunofluorescence and local field potential (LFP) recordings at various time points post-injury. Results: Our findings indicated that astrocyte-specific NLRP3 KO decreased cleaved caspase-1 colocalized with astrocytes, decreased pathogenic astrocytes and increased Postsynaptic density protein 95 (PSD95) intensity, and significantly alleviated mild TBI-induced depression-like behaviors. It also led to the upregulation of protective astrocytes and apoptosis-associated factors, including cleaved caspase-3 post-mild TBI. Additionally, astrocyte-specific NLRP3 deletion resulting in improved θ and γ power and θ-γ phase coupling in the social interaction test (SI). Notably, under mild TBI conditions, astrocyte-specific NLRP3 exhibited greater neuroprotective effects in female knockout mice compared to males. Conclusion: Astrocyte NLRP3 knockout demonstrated a protective mechanism in mice subjected to mild TBI, possibly attributed to the inhibition of pyroptosis through the NLRP3 signaling pathway in astrocytes. |
| format | Article |
| id | doaj-art-970b8dbd62274f009e55bb8e0c40afb4 |
| institution | Kabale University |
| issn | 1095-953X |
| language | English |
| publishDate | 2025-02-01 |
| publisher | Elsevier |
| record_format | Article |
| series | Neurobiology of Disease |
| spelling | doaj-art-970b8dbd62274f009e55bb8e0c40afb42025-01-24T04:44:40ZengElsevierNeurobiology of Disease1095-953X2025-02-01205106785Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice.Hui-Tao Miao0Jun Wang1Jing-Jing Shao2Rong-Xin Song3Wen-Guang Li4Jian-Kai Sun5Shi-Yan Jia6Dong-Xue Zhang7Xiao-Ming Li8Jian-Yong Zhao9Li-Min Zhang10Department of Anesthesiology, Hebei Province, Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China,; Hebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation, Cangzhou, China; Hebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research (Preparing), Cangzhou, ChinaDepartment of Orthopaedics, Tianjin Hospital, Tianjin University, Tianjin, ChinaDepartment of Anesthesiology, The First Affiliated Hospital of Zhengzhou University, Zhengzhou, ChinaDepartment of Anesthesiology, Hebei Province, Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China,Graduated School, Hebei Medical University, Shijiazhuang, ChinaGraduated School, Hebei Medical University, Shijiazhuang, ChinaHebei Province Key Laboratory of Integrated Traditional and Western Medicine in Neurological Rehabilitation, Cangzhou, ChinaDepartment of Gerontology, Cangzhou Central Hospital, Cangzhou, ChinaHebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research (Preparing), Cangzhou, ChinaHebei Key Laboratory of Integrated Traditional and Western Medicine in Osteoarthrosis Research (Preparing), Cangzhou, ChinaDepartment of Anesthesiology, Hebei Province, Cangzhou Hospital of Integrated Traditional and Western Medicine, Cangzhou, China,; Corresponding author.Background: Reports indicate that depression is a common mental health issue following traumatic brain injury (TBI). Our prior research suggests that Nucleotide-binding oligomerization domain-like receptor protein 3 (NLRP3)-related neuroinflammation, modulated by glial cells such as astrocytes, is likely to play a crucial role in the progression of anxiety and cognitive dysfunction. However, there is limited understanding of the potential of astrocytic NLRP3 in treating depression under mild TBI condition. This study aimed to determine whether astrocytic NLRP3 knockout (KO) could mitigate depressive-like behaviors following mild TBI and explore potential variations in such behaviors between genders post-mild TBI. Methods: Mild TBI was induced in mice using Feeney's weight-drop method. Behavioral assessments included neurological severity scores (NSS), social interaction test (SI), tail suspension test (TST), and forced swimming test (FST). Pathological changes were evaluated through immunofluorescence and local field potential (LFP) recordings at various time points post-injury. Results: Our findings indicated that astrocyte-specific NLRP3 KO decreased cleaved caspase-1 colocalized with astrocytes, decreased pathogenic astrocytes and increased Postsynaptic density protein 95 (PSD95) intensity, and significantly alleviated mild TBI-induced depression-like behaviors. It also led to the upregulation of protective astrocytes and apoptosis-associated factors, including cleaved caspase-3 post-mild TBI. Additionally, astrocyte-specific NLRP3 deletion resulting in improved θ and γ power and θ-γ phase coupling in the social interaction test (SI). Notably, under mild TBI conditions, astrocyte-specific NLRP3 exhibited greater neuroprotective effects in female knockout mice compared to males. Conclusion: Astrocyte NLRP3 knockout demonstrated a protective mechanism in mice subjected to mild TBI, possibly attributed to the inhibition of pyroptosis through the NLRP3 signaling pathway in astrocytes.http://www.sciencedirect.com/science/article/pii/S0969996124003875Traumatic brain injuryAstrocyteDepressionNLRP3Inflammation |
| spellingShingle | Hui-Tao Miao Jun Wang Jing-Jing Shao Rong-Xin Song Wen-Guang Li Jian-Kai Sun Shi-Yan Jia Dong-Xue Zhang Xiao-Ming Li Jian-Yong Zhao Li-Min Zhang Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice. Neurobiology of Disease Traumatic brain injury Astrocyte Depression NLRP3 Inflammation |
| title | Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice. |
| title_full | Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice. |
| title_fullStr | Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice. |
| title_full_unstemmed | Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice. |
| title_short | Astrocytic NLRP3 cKO mitigates depression-like behaviors induced by mild TBI in mice. |
| title_sort | astrocytic nlrp3 cko mitigates depression like behaviors induced by mild tbi in mice |
| topic | Traumatic brain injury Astrocyte Depression NLRP3 Inflammation |
| url | http://www.sciencedirect.com/science/article/pii/S0969996124003875 |
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