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Endothelial Cell APOE3 Regulates Neurovascular, Neuronal, and Behavioral Function.

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Area of Science:

  • Neuroscience
  • Vascular Biology
  • Genetics

Background:

  • Specialized brain endothelial cells are vital for neurovascular function.
  • Human apolipoprotein E3 (APOE3) is independently important for brain health.
  • The role of endothelial APOE3 in brain function remains largely unknown.

Purpose of the Study:

  • To investigate the impact of endothelial cell APOE3 loss on brain vascular and neural function.
  • To determine if endothelial APOE3 is essential for maintaining neurovascular integrity and cognitive processes.

Main Methods:

  • Developed genetically modified mice with inducible endothelial cell APOE3 knockdown (APOE3Cre+/-).
  • Utilized control mice (APOE3Cre-/-) for comparison.
  • Assessed neurovascular and neuronal function using biochemical, immunohistochemical, behavioral, and electrophysiological methods at 9 months of age.

Main Results:

  • Loss of endothelial APOE3 led to increased brain vascular permeability.
  • Reduced vessel coverage in the brain was observed in mice lacking endothelial APOE3.
  • Deficits in spatial memory, fear memory extinction, and disrupted cortical excitatory/inhibitory balance were evident.

Conclusions:

  • Endothelial APOE3 plays a critical role in regulating the neurovasculature.
  • Endothelial APOE3 is essential for maintaining neural circuit function and normal behavior.
  • These findings highlight a novel function of endothelial APOE3 in brain health.