Loss of Endothelial APOE4 Dysregulates Neural Function In Vivo.

IF 5 1区医学 Q1 CARDIAC & CARDIOVASCULAR SYSTEMS Journal of the American Heart Association Pub Date : 2024-11-29 DOI:10.1161/JAHA.124.035080

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

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引用次数: 0

Abstract

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 APOE4^fl/fl/Cdh5(PAC)-CreERT2^+/- and APOE4^fl/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.

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来源期刊

Journal of the American Heart Association CARDIAC & CARDIOVASCULAR SYSTEMS-

CiteScore

9.40

自引率

1.90%

发文量

1749

审稿时长

12 weeks

期刊介绍： As an Open Access journal, JAHA - Journal of the American Heart Association is rapidly and freely available, accelerating the translation of strong science into effective practice. JAHA is an authoritative, peer-reviewed Open Access journal focusing on cardiovascular and cerebrovascular disease. JAHA provides a global forum for basic and clinical research and timely reviews on cardiovascular disease and stroke. As an Open Access journal, its content is free on publication to read, download, and share, accelerating the translation of strong science into effective practice.