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Endothelial Cell APOE3 Regulates Neurovascular, Neuronal, and Behavioral Function.
Marottoli, Felecia M; Zhang, Hui; Flores-Barrera, Eden; Artur de la Villarmois, Emilce; Damen, Frederick C; Miguelez Fernández, Anabel M M; Blesson, Hannah V; Chaudhary, Rohan; Nguyen, Anthony L; Nwokeji, Amanda E; Talati, Ruju; John, Ashwin S; Madadakere, Kushi; Lutz, Sarah E; Cai, Kejia; Tseng, Kuei Y; Tai, Leon M.
Afiliação
  • Marottoli FM; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Zhang H; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Flores-Barrera E; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Artur de la Villarmois E; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Damen FC; Radiology (F.C.D., K.C.), University of Illinois at Chicago.
  • Miguelez Fernández AMM; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Blesson HV; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Chaudhary R; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Nguyen AL; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Nwokeji AE; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Talati R; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • John AS; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Madadakere K; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Lutz SE; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
  • Cai K; Radiology (F.C.D., K.C.), University of Illinois at Chicago.
  • Tseng KY; Bioengineering (K.C.), University of Illinois at Chicago.
  • Tai LM; Departments of Anatomy and Cell Biology (F.M.M., H.Z., E.F.-B., E.A.d.l.V., A.M.M.M.F., H.V.B., R.C., A.L.N., A.E.N., R.T., A.S.J., K.M., S.E.L., K.Y.T., L.M.T.), University of Illinois at Chicago.
Arterioscler Thromb Vasc Biol ; 43(10): 1952-1966, 2023 10.
Article em En | MEDLINE | ID: mdl-37650329
ABSTRACT

BACKGROUND:

Specialized brain endothelial cells and human APOE3 are independently important for neurovascular function, yet whether APOE3 expression by endothelial cells contributes to brain function is currently unknown. In the present study, we determined whether the loss of endothelial cell APOE3 impacts brain vascular and neural function.

METHODS:

We developed APOE3fl/fl/Cdh5(PAC)-CreERT2+/- (APOE3Cre+/-) and APOE3fl/fl/Cdh5(PAC)-CreERT2-/- (APOE3Cre-/-, control) mice and induced endothelial cell APOE3 knockdown with tamoxifen at ≈4 to 5 weeks of age. Neurovascular and neuronal function were evaluated by biochemistry, immunohistochemistry, behavioral testing, and electrophysiology at 9 months of age.

RESULTS:

We found that the loss of endothelial APOE3 expression was sufficient to cause neurovascular dysfunction including higher permeability and lower vessel coverage in tandem with deficits in spatial memory and fear memory extinction and a disruption of cortical excitatory/inhibitory balance.

CONCLUSIONS:

Our data collectively support the novel concept that endothelial APOE3 plays a critical role in the regulation of the neurovasculature, neural circuit function, and behavior.
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Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Células Endoteliais Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article
Texto completo
Imprimir
XML
PubMed Links
Buscar no Google

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: Encéfalo / Células Endoteliais Limite: Animals / Humans Idioma: En Ano de publicação: 2023 Tipo de documento: Article