Huan Wang1,2, Yi-Xuan Yin2,3, Dong-Mei Gong2,3, Ling-Juan Hong2, Gang Wu2, Quan Jiang2, Cheng-Kun Wang2, Pablo Blinder4, Sen Long2,5, Feng Han2,6, Ying-Mei Lu3. 1. Key Laboratory of Carbohydrate and Lipid Metabolism Research, College of Life Science and Technology, Dalian University, Dalian, China. 2. Institute of Pharmacology and Toxicology, College of Pharmaceutical Sciences, Zhejiang University, Hangzhou, China. 3. School of Medicine, Zhejiang University City College, Hangzhou, China. 4. Department of Neurobiology, George S. Wise Faculty of Life Sciences, Sagol School for Neuroscience, Tel-Aviv University, Tel Aviv, Israel. 5. Department of Pharmacy, Hangzhou No.7 People's Hospital, Mental Health Center Zhejiang University school of Medicine, Hangzhou, China. 6. Key Laboratory of Cardiovascular & Cerebrovascular Medicine, School of Pharmacy, Nanjing Medical University, Nanjing, China.
Abstract
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.
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 BTBRmice, 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 BTBRmice. The pharmacological inhibition of cathepsin B reverses the enhanced leukocyte-endothelial adhesion in the cerebral vessels of autisticmice. 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.
Authors: G Z Réus; G R Fries; L Stertz; M Badawy; I C Passos; T Barichello; F Kapczinski; J Quevedo Journal: Neuroscience Date: 2015-05-14 Impact factor: 3.590
Authors: Veronica Finisguerra; Giusy Di Conza; Mario Di Matteo; Jens Serneels; Sandra Costa; A A Roger Thompson; Els Wauters; Sarah Walmsley; Hans Prenen; Zvi Granot; Andrea Casazza; Massimiliano Mazzone Journal: Nature Date: 2015-05-18 Impact factor: 49.962
Authors: Nabangshu Das; Nikhil G Menon; Luiz G N de Almeida; Paige S Woods; Miriam L Heynen; Gregory D Jay; Barbara Caffery; Lyndon Jones; Roman Krawetz; Tannin A Schmidt; Antoine Dufour Journal: Front Pharmacol Date: 2021-12-07 Impact factor: 5.810