SOX2/DRD2 signaling pathway facilitates astrocytic dedifferentiation in cerebral ischemic mice
10.16557/j.cnki.1000-7547.2024.03.001
- VernacularTitle:SOX2/DRD2信号通路促进脑缺血小鼠星形胶质细胞去分化
- Author:
Xuyang YI
1
;
Enming KANG
;
Yanjin WANG
;
Kun ZHANG
;
Wei LIN
;
Shengxi WU
;
Yazhou WANG
Author Information
1. 空军军医大学基础医学院神经生物学教研室,西安 710032
- Keywords:
cerebral ischemia;
astrocyte;
dedifferentiation;
SOX2;
dopamine D2 receptor(DRD2);
mouse
- From:
Chinese Journal of Neuroanatomy
2024;40(3):277-286
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of dopamine receptor D2(DRD2)on astrocytic dedifferentiation based on SOX2-regulated genes in neural stem cells(NSCs)and astrocytes.Methods:Immunofluorescence staining and SOX2-GFP mice were used to examine the lineage differentiation of SOX2-positive cells during the development of cere-bral cortex.Primary NSCs/astrocytes culture,ChIP-seq and Western Blot were adopted to analyze and verify the expres-sion of candidate genes.Pharmacological manipulation,neurosphere formation,photochemical ischemia,immunofluo-rescence staining and behavior tests were adopted to evaluate the effects of activating DRD2 signaling on astrocytic dedif-ferentiation.Results:Immunofluorescence staining demonstrated the NSC-astrocyte switch of SOX2-expression in the normal development of cerebral cortex.ChIP-seq revealed enrichment of DRD2 signaling by SOX2-bound enhancers in NSCs and SOX2-bound promoters in astrocytes.Western Blot and immunofluorescence staining verified the expression of DRD2 in NSCs and reactive astrocytes.Application of quinagolide hydrocholoride(QH),an agonist of DRD2,signifi-cantly promoted astrocytic dedifferentiation both in vitro and in vivo following ischemia.In addition,quinagolide hydro-choloride treatment improved locomotion recovery.Conclusion:Activating DRD2 signaling facilitates astrocytic dedif-ferentiation and may be used to treat ischemic stroke.
