Loss of Endothelial APOE4 Dysregulates Neural Function In Vivo
Background We recently found that loss of endothelial cell APOE3 disrupts neurovascular and synaptic function. However, whether endothelial APOE4 is detrimental or protective for neural function under physiological conditions is unknown. Therefore, the goal of this study was to determine the role of...
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| Format: | Article |
| Language: | English |
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Wiley
2024-12-01
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| Series: | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
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| Online Access: | https://www.ahajournals.org/doi/10.1161/JAHA.124.035080 |
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| author | Felecia M. Marottoli Deebika Balu Eden Flores‐Barrera Emilce Artur de la Villarmois Hui Zhang Rohan Chaudhary Ruju Talati Kuei Y. Tseng Leon M. Tai |
| author_facet | Felecia M. Marottoli Deebika Balu Eden Flores‐Barrera Emilce Artur de la Villarmois Hui Zhang Rohan Chaudhary Ruju Talati Kuei Y. Tseng Leon M. Tai |
| author_sort | Felecia M. Marottoli |
| collection | DOAJ |
| description | Background We recently found that loss of endothelial cell APOE3 disrupts neurovascular and synaptic function. However, whether endothelial APOE4 is detrimental or protective for neural function under physiological conditions is unknown. Therefore, the goal of this study was to determine the role of endothelial cell APOE4 in regulating brain function in vivo. Methods and Results We developed APOE4fl/fl/Cdh5(PAC)‐CreERT2+/− and APOE4fl/fl/Cdh5(PAC)‐CreERT2−/− (control) mice. Knockdown of endothelial cell APOE4 was induced at ≈4 to 5 weeks of age. Experiments were conducted at 9 months of age to evaluate neurovascular and neuronal function via biochemistry, immunohistochemistry, behavior tests, and electrophysiology. Endothelial cell APOE4 knockdown resulted in higher neurovascular permeability, lower claudin‐5 vessel coverage, impaired trace fear memory extinction, and disruption of cortical excitatory‐inhibitory balance of synaptic activity. Conclusions Our data support the novel concept that endothelial cell APOE4 is protective for brain function when other cell types express APOE4. |
| format | Article |
| id | doaj-art-3e6a235431fc4a1e9f1c0e000b3adf6a |
| institution | Kabale University |
| issn | 2047-9980 |
| language | English |
| publishDate | 2024-12-01 |
| publisher | Wiley |
| record_format | Article |
| series | Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease |
| spelling | doaj-art-3e6a235431fc4a1e9f1c0e000b3adf6a2024-12-03T10:06:25ZengWileyJournal of the American Heart Association: Cardiovascular and Cerebrovascular Disease2047-99802024-12-01132310.1161/JAHA.124.035080Loss of Endothelial APOE4 Dysregulates Neural Function In VivoFelecia M. Marottoli0Deebika Balu1Eden Flores‐Barrera2Emilce Artur de la Villarmois3Hui Zhang4Rohan Chaudhary5Ruju Talati6Kuei Y. Tseng7Leon M. Tai8Department of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USADepartment of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USADepartment of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USADepartment of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USADepartment of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USADepartment of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USADepartment of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USADepartment of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USADepartment of Anatomy and Cell Biology University of Illinois at Chicago Chicago IL USABackground We recently found that loss of endothelial cell APOE3 disrupts neurovascular and synaptic function. However, whether endothelial APOE4 is detrimental or protective for neural function under physiological conditions is unknown. Therefore, the goal of this study was to determine the role of endothelial cell APOE4 in regulating brain function in vivo. Methods and Results We developed APOE4fl/fl/Cdh5(PAC)‐CreERT2+/− and APOE4fl/fl/Cdh5(PAC)‐CreERT2−/− (control) mice. Knockdown of endothelial cell APOE4 was induced at ≈4 to 5 weeks of age. Experiments were conducted at 9 months of age to evaluate neurovascular and neuronal function via biochemistry, immunohistochemistry, behavior tests, and electrophysiology. Endothelial cell APOE4 knockdown resulted in higher neurovascular permeability, lower claudin‐5 vessel coverage, impaired trace fear memory extinction, and disruption of cortical excitatory‐inhibitory balance of synaptic activity. Conclusions Our data support the novel concept that endothelial cell APOE4 is protective for brain function when other cell types express APOE4.https://www.ahajournals.org/doi/10.1161/JAHA.124.035080ApoE4behaviorbrain endothelial cells |
| spellingShingle | Felecia M. Marottoli Deebika Balu Eden Flores‐Barrera Emilce Artur de la Villarmois Hui Zhang Rohan Chaudhary Ruju Talati Kuei Y. Tseng Leon M. Tai Loss of Endothelial APOE4 Dysregulates Neural Function In Vivo Journal of the American Heart Association: Cardiovascular and Cerebrovascular Disease ApoE4 behavior brain endothelial cells |
| title | Loss of Endothelial APOE4 Dysregulates Neural Function In Vivo |
| title_full | Loss of Endothelial APOE4 Dysregulates Neural Function In Vivo |
| title_fullStr | Loss of Endothelial APOE4 Dysregulates Neural Function In Vivo |
| title_full_unstemmed | Loss of Endothelial APOE4 Dysregulates Neural Function In Vivo |
| title_short | Loss of Endothelial APOE4 Dysregulates Neural Function In Vivo |
| title_sort | loss of endothelial apoe4 dysregulates neural function in vivo |
| topic | ApoE4 behavior brain endothelial cells |
| url | https://www.ahajournals.org/doi/10.1161/JAHA.124.035080 |
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