Enriched environment regulates neural stem cell migration in ischemic stroke rats mediated by NT3/p75NTR signaling pathway
10.3969/j.issn.1000-4718.2025.10.011
- VernacularTitle:丰富环境通过NT3/p75NTR信号通路在缺血性卒中大鼠脑组织中发挥神经干细胞迁移调控作用
- Author:
Huiyan ZHU
1
;
Min CHEN
1
;
Chunli LI
1
Author Information
1. 新疆维吾尔自治区人民医院康复医学科,新疆 乌鲁木齐 830001
- Publication Type:Journal Article
- Keywords:
enriched environment;
neural stem cells;
ischemic stroke;
cell proliferation;
cell migration
- From:
Chinese Journal of Pathophysiology
2025;41(10):1963-1971
- CountryChina
- Language:Chinese
-
Abstract:
AIM:By establishing ischemic stroke(IS)rats and cell models,this study aimed to investigate the therapeutic effect of an enriched environment(EE)and to explore its impact on the neurotrophin 3(NT3)/p75 neuro-trophin receptor(p75NTR)signaling pathway.METHODS:The study consisted of in vivo and in vitro experiments.In vi-vo,Sprague-Dawley(SD)rats were randomly divided by weight into sham,IS,and IS+EE groups(n=10),with 8 addi-tional rats per group reserved for supplementary analyses.The IS model was established by the Longa suture occlusion method.Neurological and motor function deficits were assessed on days 1,3,7 and 14 post-modeling using the modified neurological severity score(mNSS).On days 3,7 and 14,4 additional rats from each group were sacrificed,and the whole-brain tissue was collected to measure infarct volume via 2,3,5-triphenyltetrazolium chloride(TTC)staining.On day 14,brain tissue was harvested for immunofluorescence staining to evaluate neuronal proliferation markers,while the ischemic penumbra was analyzed by Western blot for NT3/p75NTR pathway protein expression.In vitro,primary neural stem cells(NSCs)were isolated from fetal rats and cultured as neurospheres.These cells were divided into CON group and experimental groups treated with different concentrations of NT3 to evaluate the effects of NT3 on NSC proliferation and migration.Additionally,SH-SY5Y cell lines were used to establish an in vitro model of ischemic stroke through oxy-gen-glucose deprivation(OGD).These cells were treated with varying concentrations of NT3,along with CON and CON+NT3 groups,and a scratch assay was performed to assess the impact of NT3 on cell migration.RESULTS:EE significant-ly reduced neurological function scores in IS rats(P<0.05),prolonged latency in the rotarod test(P<0.05),and de-creased cerebral infarct area(P<0.05).EE further enhanced the protein expression of BrdU and Ki67 in the ischemic penumbra(P<0.05),as well as increased the co-expression of BrdU/DCX and BrdU/NeuN(P<0.05).Additionally,EE further upregulated the protein expression of NT3,p75NTR,PI3K,and Akt in the subventricular zone(SVZ)(P<0.05).In vitro,NT3(1 and 10 μg/L)significantly increased nestin expression(P<0.05)in the primary neural stem cell system.In the neural stem cell sphere system,compared to the CON group,1 μg/L NT3 markedly enhanced tubulin and phalloidin protein expression(P<0.05).In the scratch assay,1 ug/L NT3 significantly promoted the migration of both normal SH-SY5Y cells and OGD-induced SH-SY5Y cells compared to the CON group(P<0.05).CONCLUSION:Enriched envi-ronment activates the NT3/p75NTR signaling pathway,promoting the proliferation of NSCs in the SVZ and their migration to the ischemic penumbra,where they ultimately differentiate into neurons to replace those damaged,thereby contributing to the improvement of neurological function in rats with IS.
