Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice
Abstract Accumulating evidence indicates that the actin regulator cofilin is overactivated in Alzheimer’s Disease (AD), but whether this abnormality contributes to synaptic and cognitive impairments in AD is unclear. In addition, the brain region and cell types involved remain unknown. In this study...
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| Format: | Article |
| Language: | English |
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BMC
2021-07-01
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| Series: | Molecular Brain |
| Subjects: | |
| Online Access: | https://doi.org/10.1186/s13041-021-00833-3 |
| _version_ | 1818909210150174720 |
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| author | Haiwang Zhang Youssif Ben Zablah An Liu Dongju Lee Haorui Zhang Yanghong Meng Changxi Zhou Xingde Liu Yiming Wang Zhengping Jia |
| author_facet | Haiwang Zhang Youssif Ben Zablah An Liu Dongju Lee Haorui Zhang Yanghong Meng Changxi Zhou Xingde Liu Yiming Wang Zhengping Jia |
| author_sort | Haiwang Zhang |
| collection | DOAJ |
| description | Abstract Accumulating evidence indicates that the actin regulator cofilin is overactivated in Alzheimer’s Disease (AD), but whether this abnormality contributes to synaptic and cognitive impairments in AD is unclear. In addition, the brain region and cell types involved remain unknown. In this study, we specifically manipulate LIMK1, the key protein kinase that phosphorylates and inactivates cofilin, in the hippocampus of APP/PS1 transgenic mice. Using local injections of the AAV virus containing LIMK1 under the control of the CaMKIIα promoter, we show that expression of LIMK1 in hippocampal excitatory neurons increases cofilin phosphorylation (i.e., decreases cofilin activity), rescues impairments in long-term potentiation, and improves social memory in APP/PS1 mice. Our results suggest that deficits in LIMK1/cofilin signaling in the hippocampal excitatory neurons contribute to AD pathology and that manipulations of LIMK1/cofilin activity provide a potential therapeutic strategy to treat AD. |
| first_indexed | 2024-12-19T22:23:17Z |
| format | Article |
| id | doaj.art-f3038180768c41bcbdacfa76f67b8ecb |
| institution | Directory Open Access Journal |
| issn | 1756-6606 |
| language | English |
| last_indexed | 2024-12-19T22:23:17Z |
| publishDate | 2021-07-01 |
| publisher | BMC |
| record_format | Article |
| series | Molecular Brain |
| spelling | doaj.art-f3038180768c41bcbdacfa76f67b8ecb2022-12-21T20:03:34ZengBMCMolecular Brain1756-66062021-07-0114111510.1186/s13041-021-00833-3Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 miceHaiwang Zhang0Youssif Ben Zablah1An Liu2Dongju Lee3Haorui Zhang4Yanghong Meng5Changxi Zhou6Xingde Liu7Yiming Wang8Zhengping Jia9Guizhou Medical UniversityProgram in Neurosciences and Mental Health, The Hospital for Sick Children, Peter Gilgan Centre for Research and LearningThe Key Laboratory of Developmental Genes and Human Disease, Ministry of Education, School of Life Science and Technology, Southeast UniversityProgram in Neurosciences and Mental Health, The Hospital for Sick Children, Peter Gilgan Centre for Research and LearningProgram in Neurosciences and Mental Health, The Hospital for Sick Children, Peter Gilgan Centre for Research and LearningProgram in Neurosciences and Mental Health, The Hospital for Sick Children, Peter Gilgan Centre for Research and LearningDepartment of Geriatrics, The Second Medical Center and National Clinical Research Center for Geriatric Diseases, Chinese PLA General HospitalDepartment of Cardiovascular Medicine, The Second Affiliated Hospital of Guizhou University of Traditional Chinese MedicineDepartment of Psychiatry, Affiliated Hospital of Guizhou Medical UniversityProgram in Neurosciences and Mental Health, The Hospital for Sick Children, Peter Gilgan Centre for Research and LearningAbstract Accumulating evidence indicates that the actin regulator cofilin is overactivated in Alzheimer’s Disease (AD), but whether this abnormality contributes to synaptic and cognitive impairments in AD is unclear. In addition, the brain region and cell types involved remain unknown. In this study, we specifically manipulate LIMK1, the key protein kinase that phosphorylates and inactivates cofilin, in the hippocampus of APP/PS1 transgenic mice. Using local injections of the AAV virus containing LIMK1 under the control of the CaMKIIα promoter, we show that expression of LIMK1 in hippocampal excitatory neurons increases cofilin phosphorylation (i.e., decreases cofilin activity), rescues impairments in long-term potentiation, and improves social memory in APP/PS1 mice. Our results suggest that deficits in LIMK1/cofilin signaling in the hippocampal excitatory neurons contribute to AD pathology and that manipulations of LIMK1/cofilin activity provide a potential therapeutic strategy to treat AD.https://doi.org/10.1186/s13041-021-00833-3APP/PS1 transgenic miceLTPLIMK1CofilinLearning and memory |
| spellingShingle | Haiwang Zhang Youssif Ben Zablah An Liu Dongju Lee Haorui Zhang Yanghong Meng Changxi Zhou Xingde Liu Yiming Wang Zhengping Jia Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice Molecular Brain APP/PS1 transgenic mice LTP LIMK1 Cofilin Learning and memory |
| title | Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice |
| title_full | Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice |
| title_fullStr | Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice |
| title_full_unstemmed | Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice |
| title_short | Overexpression of LIMK1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in APP/PS1 mice |
| title_sort | overexpression of limk1 in hippocampal excitatory neurons improves synaptic plasticity and social recognition memory in app ps1 mice |
| topic | APP/PS1 transgenic mice LTP LIMK1 Cofilin Learning and memory |
| url | https://doi.org/10.1186/s13041-021-00833-3 |
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