title: Increased permeability of the blood-brain barrier and Alzheimer's disease-like alterations in slit-2 transgenic mice.
abstract: Alzheimer's disease (AD) is a progressive neurological disorder that primarily affects memory, and its prevalence is rising. Increasing evidence suggests that dysfunction of the blood-brain barrier (BBB) may be involved in AD and other neurodegenerative diseases. Herein, we report that the permeability of the BBB is increased and that AD-like alterations are present in Slit-2 overexpressing transgenic mice. We found that behavioral change and the corresponding molecular diagnostic markers of AD, such as hippocampal neuron apoptosis, amyloid-β (Aβ) protein deposition, and acetylcholinesterase expression, were increased in the Slit-2 transgenic mice. Moreover, the endothelial cells were dysfunctional, the size of the lateral ventricle cavity increased, and the permeability of the BBB increased. Additionally, there was an increased serum level of glutamate indicating that the BBB is related to AD. Finally, histopathological analysis of other organs in the Slit-2 overexpressing mice did not show any marked abnormalities. These findings demonstrate that Slit2 overexpression may be responsible for AD-like alterations and the increased BBB permeability in these mice. Our study provides a potential novel mechanism for the development of AD.
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Jiang-chao
authors.initials: JC
authors.lastname: Li
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Lu
authors.initials: L
authors.lastname: Han
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Yin-xin
authors.initials: YX
authors.lastname: Wen
authors.affiliation: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Yong-xia
authors.initials: YX
authors.lastname: Yang
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Li
authors.affiliation: The Third People's Hospital of Foshan, Foshan, China.
authors.forename: Xue-song
authors.initials: XS
authors.lastname: Li
authors.affiliation: The Third People's Hospital of Foshan, Foshan, China.
authors.forename: Chang-jiang
authors.initials: CJ
authors.lastname: Zhao
authors.affiliation: Dongguan Xinyong Hospital, Dongguan, China.
authors.forename: Ting-yu
authors.initials: TY
authors.lastname: Wang
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Hui
authors.initials: H
authors.lastname: Chen
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Ying
authors.initials: Y
authors.lastname: Liu
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Cui-ling
authors.initials: CL
authors.lastname: Qi
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Xiao-dong
authors.initials: XD
authors.lastname: He
authors.affiliation: School of Basic Courses, Guangdong Pharmaceutical University, Guangzhou, Guangdong, China.
authors.forename: Qu-liang
authors.initials: QL
authors.lastname: Gu
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Yu-xiang
authors.initials: YX
authors.lastname: Ye
authors.affiliation: Guangdong Key Laboratory of Laboratory Animals/Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong, China.
authors.forename: Yu
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Guangdong Key Laboratory of Laboratory Animals/Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong, China.
authors.forename: Ren
authors.initials: R
authors.lastname: Huang
authors.affiliation: Guangdong Key Laboratory of Laboratory Animals/Guangdong Laboratory Animals Monitoring Institute, Guangzhou, Guangdong, China.
authors.forename: Yu-e
authors.initials: YE
authors.lastname: Wu
authors.affiliation: Anti-Stress and Health Research Center, Pharmacy College, Jinan University, Guagnzhou, China.
authors.forename: Rong-rong
authors.initials: RR
authors.lastname: He
authors.affiliation: Anti-Stress and Health Research Center, Pharmacy College, Jinan University, Guagnzhou, China.
authors.forename: Hiroshi
authors.initials: H
authors.lastname: Kurihara
authors.affiliation: Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Xiao-yu
authors.initials: XY
authors.lastname: Song
authors.affiliation: Key Laboratory of Cell Biology, Ministry of Public Health, Key Laboratory of Medical Cell Biology, Ministry of Education, China Medical University, Shenyang, China.
authors.forename: Liu
authors.initials: L
authors.lastname: Cao
authors.affiliation: Vascular Biology Research Institute, Guangdong Pharmaceutical University, Guangzhou, China.
authors.forename: Li-jing
authors.initials: LJ
authors.lastname: Wang
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000544:Alzheimer Disease / Q000097:blood / Q000235:genetics* / Q000473:pathology*; D016564:Amyloid beta-Protein Precursor / Q000235:genetics; D000818:Animals; D018916:Blood-Aqueous Barrier / Q000503:physiopathology* / Q000648:ultrastructure; D002199:Capillary Permeability / Q000235:genetics*; D004195:Disease Models, Animal; D005260:Female; D005786:Gene Expression Regulation / Q000235:genetics*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D046529:Microscopy, Electron, Transmission; D008875:Middle Aged; D009419:Nerve Tissue Proteins / Q000235:genetics*; D019906:Nuclear Magnetic Resonance, Biomolecular; D000098552:Slit Homolog 2 Protein
chemical_list: D016564:Amyloid beta-Protein Precursor; D036341:Intercellular Signaling Peptides and Proteins; D009419:Nerve Tissue Proteins; D000098552:Slit Homolog 2 Protein
keywords: Alzheimer's disease; Slit homolog 2 protein; blood-brain barrier; transgenic mice