The role of <scp>LINC</scp>00094/miR‐224‐5p (miR‐497‐5p)/Endophilin‐1 axis in Memantine mediated protective effects on blood‐brain barrier in <scp>AD</scp> microenvironment

Abstract

Abstract The dysfunction of the blood‐brain barrier ( BBB ) is one of the main pathological features of Alzheimer's disease ( AD ). Memantine ( MEM ), an N ‐methyl‐ d ‐aspartate ( NMDA ) receptor antagonist, has been reported that been used widely for AD therapy. This study was performed to demonstrate the role of the MEM in regulating BBB permeability in AD microenvironment as well as its possible mechanisms. The present study showed that LINC 00094 was dramatically increased in Abeta 1‐42 ‐incubated microvascular endothelial cells ( EC s) of BBB model in vitro. Besides, it was decreased in MEM ‐incubated EC s. Silencing LINC 00094 significantly decreased BBB permeability, meanwhile up‐regulating the expression of ZO ‐1, occludin and claudin‐5. Furthermore, silencing LINC 00094 enhance the effect of MEM on decreasing BBB permeability in AD microenvironment. The analysis of the mechanism demonstrated that reduction of LINC 00094 inhibited Endophilin‐1 expression by up‐regulating miR‐224‐4p/miR‐497‐5p, promoted the expression of ZO ‐1, occludin and claudin‐5, and ultimately alleviated BBB permeability in AD microenvironment. Taken together, the present study suggests that the MEM / LINC 00094/miR‐224‐5p (miR‐497‐5p)/Endophilin‐1 axis plays a crucial role in the regulation of BBB permeability in AD microenvironment. Silencing LINC 00094 combined with MEM provides a novel target for the therapy of AD .