The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption
Acute sleep deprivation (ASD) impairs memory formation, but the underlying mechanisms remain unclear. In this study, we employed an ASD model combined with fear conditioning to investigate these mechanisms. mRNA sequencing revealed upregulated expression of Transient Receptor Potential Vanilloid 4 (...
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Elsevier
2025-06-01
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| Series: | Cell Insight |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S2772892725000148 |
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| author | Meimei Guo Feiyang Zhang Sha Liu Yi Zhang Lesheng Wang Jian Song Wei Wei Xiang Li |
| author_facet | Meimei Guo Feiyang Zhang Sha Liu Yi Zhang Lesheng Wang Jian Song Wei Wei Xiang Li |
| author_sort | Meimei Guo |
| collection | DOAJ |
| description | Acute sleep deprivation (ASD) impairs memory formation, but the underlying mechanisms remain unclear. In this study, we employed an ASD model combined with fear conditioning to investigate these mechanisms. mRNA sequencing revealed upregulated expression of Transient Receptor Potential Vanilloid 4 (TRPV4), a nonselective Ca2+-permeable cation channel critical for calcium signaling, in mice with ASD-induced memory impairments. Notably, TRPV4 knockdown reversed ASD-induced memory deficits. ASD was associated with increased intracellular Ca2+ concentrations, reduced spine density, and decreased expression of postsynaptic density protein 95 (PSD95), a key regulator of synaptic plasticity. These findings suggest that ASD may cause Ca2+ overload, leading to disrupted synaptic plasticity and impaired learning and memory. Importantly, TRPV4 knockdown significantly reduced Ca2+ concentrations, mitigated synaptic plasticity impairments, and contributed to memory restoration. Together, these findings demonstrate a protective role of TRPV4 knockdown against ASD-induced memory deficits and highlight TRPV4 as a potential therapeutic target for memory impairment associated with ASD. |
| format | Article |
| id | doaj-art-75d3fd9a0e3243289ffcda05828a4a23 |
| institution | OA Journals |
| issn | 2772-8927 |
| language | English |
| publishDate | 2025-06-01 |
| publisher | Elsevier |
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| series | Cell Insight |
| spelling | doaj-art-75d3fd9a0e3243289ffcda05828a4a232025-08-20T02:07:47ZengElsevierCell Insight2772-89272025-06-014310024010.1016/j.cellin.2025.100240The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruptionMeimei Guo0Feiyang Zhang1Sha Liu2Yi Zhang3Lesheng Wang4Jian Song5Wei Wei6Xiang Li7Brain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaBrain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaDepartment of General Practice, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaBrain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaBrain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, ChinaDepartment of Neurosurgery, General Hospital of Central Theater Command, Wuhan 430070, Hubei, China; The Second School of Clinical Medicine, Wuhan University, Wuhan 430071, Hubei, China; The First School of Clinical Medicine, Southern Medical University Guangzhou 510515, Guangdong, China; Corresponding author. Department of Neurosurgery, General Hospital of Central Theater Command, Wuhan 430070, Hubei, China.Brain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China; Corresponding author. Brain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China.Brain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China; Department of Neurosurgery, Zhongnan Hospital of Wuhan University, Wuhan 430071, Hubei, China; Frontier Science Center for Immunology and Metabolism, Wuhan University, Wuhan 430071, Hubei, China; Medical Research Institute, Wuhan University, Wuhan 430071, Hubei, China; Sino-Italian Ascula Brain Science Joint Laboratory, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China; Corresponding author. Brain Research Center, Zhongnan Hosptial of Wuhan University, Wuhan 430071, Hubei, China.Acute sleep deprivation (ASD) impairs memory formation, but the underlying mechanisms remain unclear. In this study, we employed an ASD model combined with fear conditioning to investigate these mechanisms. mRNA sequencing revealed upregulated expression of Transient Receptor Potential Vanilloid 4 (TRPV4), a nonselective Ca2+-permeable cation channel critical for calcium signaling, in mice with ASD-induced memory impairments. Notably, TRPV4 knockdown reversed ASD-induced memory deficits. ASD was associated with increased intracellular Ca2+ concentrations, reduced spine density, and decreased expression of postsynaptic density protein 95 (PSD95), a key regulator of synaptic plasticity. These findings suggest that ASD may cause Ca2+ overload, leading to disrupted synaptic plasticity and impaired learning and memory. Importantly, TRPV4 knockdown significantly reduced Ca2+ concentrations, mitigated synaptic plasticity impairments, and contributed to memory restoration. Together, these findings demonstrate a protective role of TRPV4 knockdown against ASD-induced memory deficits and highlight TRPV4 as a potential therapeutic target for memory impairment associated with ASD.http://www.sciencedirect.com/science/article/pii/S2772892725000148Learning and memorySleep deprivation (SD)Transient receptor potential vanilloid 4 (TRPV4)Postsynaptic density protein 95 (PSD95)Synaptic plasticity |
| spellingShingle | Meimei Guo Feiyang Zhang Sha Liu Yi Zhang Lesheng Wang Jian Song Wei Wei Xiang Li The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption Cell Insight Learning and memory Sleep deprivation (SD) Transient receptor potential vanilloid 4 (TRPV4) Postsynaptic density protein 95 (PSD95) Synaptic plasticity |
| title | The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption |
| title_full | The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption |
| title_fullStr | The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption |
| title_full_unstemmed | The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption |
| title_short | The role of TRPV4 in acute sleep deprivation-induced memory impairment: Mechanisms of calcium dysregulation and synaptic plasticity disruption |
| title_sort | role of trpv4 in acute sleep deprivation induced memory impairment mechanisms of calcium dysregulation and synaptic plasticity disruption |
| topic | Learning and memory Sleep deprivation (SD) Transient receptor potential vanilloid 4 (TRPV4) Postsynaptic density protein 95 (PSD95) Synaptic plasticity |
| url | http://www.sciencedirect.com/science/article/pii/S2772892725000148 |
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