Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in mice
Abstract Astrocyte elevated gene-1 (AEG-1) has been characterized as an oncogene promoting the progression of various tumors. The role of AEG-1 in neurological diseases was highlighted by recent researches. However, the physiological function of AEG-1 remains elusive. Our study aimed to investigate...
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Nature Publishing Group
2025-03-01
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| Series: | Cell Death and Disease |
| Online Access: | https://doi.org/10.1038/s41419-025-07508-0 |
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| author | Ya-he Wang Ning Zhou Pan-pan Wan Xin-tong Li Chun-yang Yu Jinjiang Chou Zong-yi Feng Lian-xiang Zhang Juan-juan Li Bao-cong Yu Zhen-ning Tang Kun-mei Liu Le Guo |
| author_facet | Ya-he Wang Ning Zhou Pan-pan Wan Xin-tong Li Chun-yang Yu Jinjiang Chou Zong-yi Feng Lian-xiang Zhang Juan-juan Li Bao-cong Yu Zhen-ning Tang Kun-mei Liu Le Guo |
| author_sort | Ya-he Wang |
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| description | Abstract Astrocyte elevated gene-1 (AEG-1) has been characterized as an oncogene promoting the progression of various tumors. The role of AEG-1 in neurological diseases was highlighted by recent researches. However, the physiological function of AEG-1 remains elusive. Our study aimed to investigate the physiological role of AEG-1 in the central nervous system by generating a mouse model with specific deletion of Aeg-1 in the hippocampus and neocortex (Aeg-1 fl/flCre+ mice). Behavioral assessments revealed that Aeg-1 deficiency caused impaired learning and memory capabilities in juvenile and adult mice. Depressive-like behaviors were also observed in Aeg-1 fl/flCre+ mice. Gene Ontology (GO) enrichment analyses indicated that AEG-1 was involved in the neuronal morphogenesis. Interestingly, Aeg-1 knockout was irrelevant to the neuron loss but reduced the dendritic length and the dendritic spines density in hippocampus. Electrophysiological analyses showed a decreased response of paired-pulse facilitation (PPF) and a compromised efficiency of excitatory synaptic transmission following Aeg-1 deletion in hippocampus. In conclusion, our findings suggest that Aeg-1 deficiency in the hippocampus and neocortex leads to learning and memory impairments and depression in mice, which is mediated by the abnormalities of neuronal morphology and the impaired synaptic functions. |
| format | Article |
| id | doaj-art-dd150e56960944ef94d8f4498ccbbc50 |
| institution | OA Journals |
| issn | 2041-4889 |
| language | English |
| publishDate | 2025-03-01 |
| publisher | Nature Publishing Group |
| record_format | Article |
| series | Cell Death and Disease |
| spelling | doaj-art-dd150e56960944ef94d8f4498ccbbc502025-08-20T02:10:13ZengNature Publishing GroupCell Death and Disease2041-48892025-03-0116111110.1038/s41419-025-07508-0Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in miceYa-he Wang0Ning Zhou1Pan-pan Wan2Xin-tong Li3Chun-yang Yu4Jinjiang Chou5Zong-yi Feng6Lian-xiang Zhang7Juan-juan Li8Bao-cong Yu9Zhen-ning Tang10Kun-mei Liu11Le Guo12Ningxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityDepartment of Cell and Molecular Biology, Karolinska InstitutetNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityDepartment of Surgical Oncology, General Hospital of Ningxia Medical UniversityNingxia Key Laboratory of Cerebrocranial Disease, Ningxia Medical UniversityNingxia Key Laboratory of Clinical and Pathogenic Microbiology, General Hospital of Ningxia Medical UniversityAbstract Astrocyte elevated gene-1 (AEG-1) has been characterized as an oncogene promoting the progression of various tumors. The role of AEG-1 in neurological diseases was highlighted by recent researches. However, the physiological function of AEG-1 remains elusive. Our study aimed to investigate the physiological role of AEG-1 in the central nervous system by generating a mouse model with specific deletion of Aeg-1 in the hippocampus and neocortex (Aeg-1 fl/flCre+ mice). Behavioral assessments revealed that Aeg-1 deficiency caused impaired learning and memory capabilities in juvenile and adult mice. Depressive-like behaviors were also observed in Aeg-1 fl/flCre+ mice. Gene Ontology (GO) enrichment analyses indicated that AEG-1 was involved in the neuronal morphogenesis. Interestingly, Aeg-1 knockout was irrelevant to the neuron loss but reduced the dendritic length and the dendritic spines density in hippocampus. Electrophysiological analyses showed a decreased response of paired-pulse facilitation (PPF) and a compromised efficiency of excitatory synaptic transmission following Aeg-1 deletion in hippocampus. In conclusion, our findings suggest that Aeg-1 deficiency in the hippocampus and neocortex leads to learning and memory impairments and depression in mice, which is mediated by the abnormalities of neuronal morphology and the impaired synaptic functions.https://doi.org/10.1038/s41419-025-07508-0 |
| spellingShingle | Ya-he Wang Ning Zhou Pan-pan Wan Xin-tong Li Chun-yang Yu Jinjiang Chou Zong-yi Feng Lian-xiang Zhang Juan-juan Li Bao-cong Yu Zhen-ning Tang Kun-mei Liu Le Guo Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in mice Cell Death and Disease |
| title | Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in mice |
| title_full | Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in mice |
| title_fullStr | Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in mice |
| title_full_unstemmed | Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in mice |
| title_short | Hippocampus- and neocortex-specific deletion of Aeg-1 causes learning memory impairment and depression in mice |
| title_sort | hippocampus and neocortex specific deletion of aeg 1 causes learning memory impairment and depression in mice |
| url | https://doi.org/10.1038/s41419-025-07508-0 |
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