Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer’s mouse models
Abstract Background Microglia are brain-resident macrophages that play a crucial role in synapse pruning during the development and progression of various neuropsychiatric disorders, including autism spectrum disorder (ASD) and Alzheimer’s disease (AD). Mechanistically, CD47 protein acts as a potent...
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2025-03-01
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| Online Access: | https://doi.org/10.1186/s13578-025-01378-x |
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| author | Wenjie Hu Mengting Chen Yuxue Lin Hui Zhang Li Sun Wei Shao Yuping Ye Yujie Cheng Shanshan Zhou Panpan Hu Xingqi Wu Yin Xu Kai Wang |
| author_facet | Wenjie Hu Mengting Chen Yuxue Lin Hui Zhang Li Sun Wei Shao Yuping Ye Yujie Cheng Shanshan Zhou Panpan Hu Xingqi Wu Yin Xu Kai Wang |
| author_sort | Wenjie Hu |
| collection | DOAJ |
| description | Abstract Background Microglia are brain-resident macrophages that play a crucial role in synapse pruning during the development and progression of various neuropsychiatric disorders, including autism spectrum disorder (ASD) and Alzheimer’s disease (AD). Mechanistically, CD47 protein acts as a potent ‘do not eat me’ signal, protecting synapses from phagocytosis by microglia. However, the functional role of the upregulated neuronal CD47 signal under both physiological and pathological conditions remains unclear. Results We utilized an adeno-associated virus gene expression system to induce neuron-specific overexpression of CD47 in wild-type and 5xFAD mice, assessing its effects on microglial synaptic phagocytosis and mouse behaviors. Our results indicate that neuronal CD47 induces ASD-like behaviors and synaptic pruning defects, while promoting behavioral disinhibition and improving memory in wild-type mice. Single-nucleus RNA sequencing was employed to profile gene expression patterns in subpopulations of neurons and microglia. Notably, neuronal CD47 enhances synaptic pathways in neurons and particularly shifts microglial subpopulations from a disease-associated state to a homeostatic state. Additionally, neuronal CD47 reduces excessive microglial synaptic phagocytosis induced by Aβ pathology in 5xFAD mice. Conclusion Our study provides evidence that neuronal CD47 overexpression results in synaptic pruning defects and is involved in the pathogenesis of ASD, while also playing a beneficial role in mitigating excessive synaptic loss in Alzheimer’s disease. |
| format | Article |
| id | doaj-art-46fb6c208a6f449ba74d04d7cd87ea57 |
| institution | OA Journals |
| issn | 2045-3701 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | BMC |
| record_format | Article |
| series | Cell & Bioscience |
| spelling | doaj-art-46fb6c208a6f449ba74d04d7cd87ea572025-08-20T02:10:20ZengBMCCell & Bioscience2045-37012025-03-0115111510.1186/s13578-025-01378-xNeuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer’s mouse modelsWenjie Hu0Mengting Chen1Yuxue Lin2Hui Zhang3Li Sun4Wei Shao5Yuping Ye6Yujie Cheng7Shanshan Zhou8Panpan Hu9Xingqi Wu10Yin Xu11Kai Wang12Department of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical UniversitySchool of Mental Health and Psychological Sciences, Anhui Medical UniversitySchool of Mental Health and Psychological Sciences, Anhui Medical UniversitySchool of Mental Health and Psychological Sciences, Anhui Medical UniversitySchool of Mental Health and Psychological Sciences, Anhui Medical UniversitySchool of Mental Health and Psychological Sciences, Anhui Medical UniversitySchool of Mental Health and Psychological Sciences, Anhui Medical UniversitySchool of Mental Health and Psychological Sciences, Anhui Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical UniversityDepartment of Neurology, The First Affiliated Hospital of Anhui Medical University, Anhui Medical UniversityAbstract Background Microglia are brain-resident macrophages that play a crucial role in synapse pruning during the development and progression of various neuropsychiatric disorders, including autism spectrum disorder (ASD) and Alzheimer’s disease (AD). Mechanistically, CD47 protein acts as a potent ‘do not eat me’ signal, protecting synapses from phagocytosis by microglia. However, the functional role of the upregulated neuronal CD47 signal under both physiological and pathological conditions remains unclear. Results We utilized an adeno-associated virus gene expression system to induce neuron-specific overexpression of CD47 in wild-type and 5xFAD mice, assessing its effects on microglial synaptic phagocytosis and mouse behaviors. Our results indicate that neuronal CD47 induces ASD-like behaviors and synaptic pruning defects, while promoting behavioral disinhibition and improving memory in wild-type mice. Single-nucleus RNA sequencing was employed to profile gene expression patterns in subpopulations of neurons and microglia. Notably, neuronal CD47 enhances synaptic pathways in neurons and particularly shifts microglial subpopulations from a disease-associated state to a homeostatic state. Additionally, neuronal CD47 reduces excessive microglial synaptic phagocytosis induced by Aβ pathology in 5xFAD mice. Conclusion Our study provides evidence that neuronal CD47 overexpression results in synaptic pruning defects and is involved in the pathogenesis of ASD, while also playing a beneficial role in mitigating excessive synaptic loss in Alzheimer’s disease.https://doi.org/10.1186/s13578-025-01378-xCD47MicrogliaAlzheimer’s diseaseAutism spectrum disorderNeuron-microglia interactions |
| spellingShingle | Wenjie Hu Mengting Chen Yuxue Lin Hui Zhang Li Sun Wei Shao Yuping Ye Yujie Cheng Shanshan Zhou Panpan Hu Xingqi Wu Yin Xu Kai Wang Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer’s mouse models Cell & Bioscience CD47 Microglia Alzheimer’s disease Autism spectrum disorder Neuron-microglia interactions |
| title | Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer’s mouse models |
| title_full | Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer’s mouse models |
| title_fullStr | Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer’s mouse models |
| title_full_unstemmed | Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer’s mouse models |
| title_short | Neuronal CD47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild-type and Alzheimer’s mouse models |
| title_sort | neuronal cd47 induces behavioral alterations and ameliorates microglial synaptic pruning in wild type and alzheimer s mouse models |
| topic | CD47 Microglia Alzheimer’s disease Autism spectrum disorder Neuron-microglia interactions |
| url | https://doi.org/10.1186/s13578-025-01378-x |
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