Arginase1 Knockdown Improves Cognitive Function by Enhancing Aβ Degradation and Reducing Neuroinflammation in APP/PS1 Mouse
10.13471/j.cnki.j.sun.yat-sen.univ（med.sci）.2022.0303
- VernacularTitle:Arginase1敲低通过增强Aβ降解和减轻神经炎症改善APP/PS1小鼠认知功能
- Author:
Qing-bo WANG
1
;
Jiao-ling TANG
1
;
Kai-hua GUO
1
;
Jie XU
1
Author Information
1. Department of Anatomy and Neurobiology， Zhongshan School of Medicine， Sun Yat-sen University，Guangzhou 510080， China
- Publication Type:Journal Article
- Keywords:
Arginase1 （Arg1）;
APP/PS1 transgenic mice;
amyloid β-protein （Aβ）
- From:
Journal of Sun Yat-sen University(Medical Sciences)
2022;43(3):352-360
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo investigate the effect of the M2 microglia marker Arginase1 （Arg1） knockdown on cognitive function in APP/PS1 transgenic mouse model of Alzheimer's disease （AD）. MethodsArginase1 genetically engineered mice were used and divided into C57BL/6 control group （WT）， Arginase1 low expression group （Arg1+/-）， Alzheimer's disease mouse model group （APP/PS1）， Arginase1， APP/PS1 transgenic mice Arginase1 low expression group （Arg1+/-； APP/PS1）. We used open field test （OFT） to assess the autonomous activity and adaptive capacity of mice； morris water maze experiment （MWM） to evaluate learning and memory function of mice； thioflavine-S staining to observe the brain amyloid β-protein （Aβ） deposition in mice； immunofluorescence staining to detect the expression of microglia markers ionized calcium-binding adaptor molecule 1 （Iba1）， transmembrane protein 119 （Tmem119） and lysosomal protein （CD68）； Elisa to determine Aβ1-40 and Aβ1-42 expression in hippocampal and cortical tissues； and protein immunoblot （Western blot） to measure the expression of amyloid precursor protein （APP）， beta-site APP-cleaving enzyme （BACE）， enkephalinase （NEP）， and interleukin-1β （IL-1β）. ResultsCompared with APP/PS1 group， Arg1+/-； APP/PS1 group showed significantly increased duration and frequency in central area （P<0.00 1）； significantly reduced escape latency （P<0.001）， significantly increased dwell time， path length in the target quadrant and times of crossing the platform （all P<0.05）； significant decrease of Aβ deposition in the hippocampus （P<0.000 1） and significant increased expression of CD68 by microglia in the hippocampal region （P=0.039 2， P=0.000 3）； decreased levels of Aβ1-40， Aβ1-42， APP， IL-1β and increased expression of NEP protein （P<0.000 1）. No significant difference in BACE protein expression （P=0.497 7） was found. ConclusionDown-regulation of Arg1 may promote microglia activation in the brain， up-regulate the level of Aβ-degrading enzyme NEP， reduce Aβ deposition and neuroinflammation in the brain， thus improve the spatial learning capacity of APP/PS1 mouse model of AD.
