Open AccessCathepsin B inhibition ameliorates leukocyte‐endothelial adhesion in the BTBR mouse model of autism
Author(s) -
Wang Huan,
Yin YiXuan,
Gong DongMei,
Hong LingJuan,
Wu Gang,
Jiang Quan,
Wang ChengKun,
Blinder Pablo,
Long Sen,
Han Feng,
Lu YingMei
Publication year - 2019
Publication title -
cns neuroscience and therapeutics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.403
H-Index - 69
eISSN - 1755-5949
pISSN - 1755-5930
DOI - 10.1111/cns.13074
Subject(s) - chemokine , cathepsin b , cell adhesion molecule , cell adhesion , immunology , inflammation , adhesion , chemistry , microbiology and biotechnology , medicine , biology , biochemistry , organic chemistry , enzyme
Summary Aims Autism spectrum disorder (ASD) is a wide range of neurodevelopmental disorders involving deficits in social interaction and communication. Unfortunately, autism remains a scientific and clinical challenge owing to the lack of understanding the cellular and molecular mechanisms underlying it. This study aimed to investigate the pathophysiological mechanism underlying leukocyte‐endothelial adhesion in autism‐related neurovascular inflammation. Methods Male BTBR T+tf/J mice were used as an autism model. The dynamic pattern of leukocyte‐endothelial adhesion in mouse cerebral vessels was detected by two‐photon laser scanning microscopy (TPLSM). Using FACS, RT‐PCR, and Western blotting, we explored the expression of cell adhesion molecules, the mRNA expression of endothelial chemokine, the protein levels of cathepsin B, and inflammatory mediators. Results We found a significant increase in leukocyte‐endothelial adhesion in BTBR mice, accompanied by elevated expression of the adhesion molecule neutrophils CD11b and endothelial ICAM‐1. Our data further indicate that elevated neutrophil cathepsin B levels contribute to elevated endothelial chemokine CXCL7 levels in BTBR mice. The pharmacological inhibition of cathepsin B reverses the enhanced leukocyte‐endothelial adhesion in the cerebral vessels of autistic mice. Conclusion Our results revealed the prominent role of cathepsin B in modulating leukocyte‐endothelial adhesion during autism‐related neurovascular inflammation and identified a promising novel approach for autism treatment.