Effects of ADAM10 inhibitor on synaptic structure and blood-brain barrier permeability in rats with autism-like behavior
10.16016/j.2097-0927.202404037
- VernacularTitle:ADAM10抑制剂对孤独症样行为大鼠突触结构和血脑屏障通透性的影响
- Author:
Jingyuan YANG
1
;
Xiaoli LI
;
Chunyan WU
;
Yali BAI
;
Jie CHEN
;
Li CHEN
Author Information
1. 400014 重庆,重庆医科大学附属儿童医院儿童生长发育与心理健康中心,国家儿童健康与疾病临床医学研究中心,儿童发育疾病研究教育部重点实验室,儿童神经发育与认知障碍重庆市重点实验室
- Keywords:
autism spectrum disorder;
a disintegrin and metalloprotease domain 10;
blood-brain barrier;
synapsis
- From:
Journal of Army Medical University
2024;46(21):2457-2466
- CountryChina
- Language:Chinese
-
Abstract:
Objective To investigate the effects of a disintegrin and metalloprotease domain 10(ADAM10)inhibitor on synaptic structure and blood-brain barrier(BBB)permeability in rats with autism-like behavior.Methods A total of 50 male offspring rats with prenatal exposure to valproic acid(VPA)to induce autism-like behavior were randomly divided into VPA group and ADAM 10 inhibitor,TAT-Pro-ADAM10(709-729)group(TAT-Pro group),with 25 rats in each group.And another 25 offspring male rats induced by normal saline during pregnancy served as control group(CON group).The TAT-Pro group was given intraperitoneal injection on postnatal day 20 with 3 nmol/g TAT-Pro-ADAM10(709-729),and equal volumes of normal saline were given to the CON and VPA groups.The changes of body mass and tail length of offspring rats were measured and recorded during modeling.Western blotting was performed to detect the protein levels of ADAM10,vascular endothelial cadherin(VE-Cad),Occludin,zonula occludens-1(ZO-1),post-synaptic density protein-95(PSD95),and synaptophysin(SYN)in the hippocampal tissue of the offspring rats in 24 h after administration.The expression of ZO-1 protein was further verified by immunofluorescence assay.Behavioral tests were conducted from postnatal day 24,including open field,grooming,three-chamber social interaction,and water maze tests.The density of dendritic spines in hippocampal tissue in the offspring rats on postnatal day 28 was detected by Golgi staining.Results Compared with the VPA group,the TAT-Pro group showed no significant changes in body weight and tail length,but significantly improved repetitive stereotyped behaviors,social skills and learning memory ability(P＜0.05),reduced protein levels of ADAM10 and PSD95 in hippocampal tissues(P＜0.05),and elevated levels of VE-cad and Occludin(P＜0.05).The density of dendritic spines was significantly reduced(P＜0.05),and the number of immature dendritic spines also decreased in the TAT-Pro group than the VPA group.Conclusion Inhibition of ADAM10 overexpression during the critical period of synaptic development can alleviate learning and memory dysfunctions in VPA-induced rats with autism-like behavior,and has a certain restorative effect on abnormal synaptic structures and blood-brain barrier permeability.
