Brain endothelial LRP1 maintains blood\u2013brain barrier integrity

Steffen E Storck,Claus U Pietrzik,Magdalena Kurtyka

doi:10.1186/s12987-021-00260-5

Abstract

The entry of blood-borne molecules into the brain is restricted by the blood–brain barrier (BBB). Various physical, transport and immune properties tightly regulate molecule movement between the blood and the brain to maintain brain homeostasis. A recent study utilizing a pan-endothelial, constitutive Tie2-Cre showed that paracellular passage of blood proteins into the brain is governed by endocytic and cell signaling protein low-density lipoprotein receptor–related protein 1 (LRP1). Taking advantage of conditional Slco1c1-CreERT2 specific to CNS endothelial cells and choroid plexus epithelial cells we now supplement previous results and show that brain endothelial Lrp1 ablation results in protease-mediated tight junction degradation, P-glycoprotein (P-gp) reduction and a loss of BBB integrity.

Highlights

Neuronal function requires tight regulation of the cerebral microenvironment, which is achieved through specialized brain barriers such as the blood–brain barrier (BBB) [1]
We developed Lrp1lox/lox; Slco1c1-CreERT2 mice that allow the deletion of Lrp1 in brain endothelial cells in adult mice
Using Lrp1lox/lox; Slco1c1-CreERT2 mice, we sought to investigate whether a knockout of Lrp1 in CNS endothelial cells has any effect on barrier integrity of the BBB

Summary

Introduction

Neuronal function requires tight regulation of the cerebral microenvironment, which is achieved through specialized brain barriers such as the blood–brain barrier (BBB) [1]. The second question remains regards the specificity of the Cre mouse line that was used in the study: how does a constitutive and global deletion of Lrp1 in all endothelial cells contributes to the brain-related findings described in Nikolakopoulou et al.?

Results

Conclusion