Effect of Oleracein E on the senescence of neural stem cells in vascular dementia rats

XU Jiang; LANG Hai-li; LU Qi; SHI Yi-chuan; WU Lei; HU Guo-wen

doi:10.13798/j.issn.1009-153X.2025.02.006

Abstract：Objective To investigate the effects of Oleracein E(OE)on the senescence of hippocampal neural stem cells(H-NSCs)in vascular dementia(VD)rats.Methods Thirty adult male Sprague-Dawley rats were randomly divided into three groups:sham,VD,and OE.A permanent bilateral common carotid artery occlusion model was used to simulate hippocampal neuronal injury in VD rats.The OE group received intragastric administration of OE suspension(15 mg/kg/day)once daily for 2 months.Cognitive function was assessed using the Morris water maze test.Senescence levels of H-NSCs were evaluated via SA-β-gal activity staining and immunofluorescence staining for aging-related proteins(γ-H2A.X and p16INK4a).Western blotting was performed to measure the expression levels of p-ERK,ERK,p-AMPK,AMPK,p-mTOR,and mTOR in H-NSCs.Results The Morris water maze test revealed that spatial learning and memory function in the OE group were significantly better than those in the VD group(P<0.05).SA-β-gal staining and immunofluorescence staining for γ-H2A.X and p16INK4a demonstrated markedly reduced senescence of H-NSCs in the OE group compared to the VD group(P<0.05).Western blot analysis showed that the expression levels of p-ERK and p-mTOR in H-NSCs were significantly lower in the OE group than in the VD group(P<0.05),while p-AMPK expression was significantly higher(P<0.05).Conclusion OE attenuates H-NSC senescence and improves cognitive dysfunction in VD rats,potentially through inhibition of ERK phosphorylation,promotion of AMPK phosphorylation,and suppression of the mTOR signaling pathway.