Adenosine improves learning memory in thromboembolic stroke rats through PI3K/Akt/CREB signalling pathway
10.16557/j.cnki.1000-7547.2025.04.006
- VernacularTitle:腺苷通过PI3K/Akt/CREB信号通路改善血栓栓塞脑卒中大鼠的学习记忆能力
- Author:
Jiahao DONG
1
;
Mingrui LIU
;
Cheng YUAN
;
Hao WU
;
Zihan GAO
;
Hui LIU
;
Yingjiao LIU
Author Information
1. 江西中医药大学:药学院,南昌 330004
- Publication Type:Journal Article
- Keywords:
adenosine;
PI3K/Akt/CREB pathway;
thromboembolic stroke model;
glutamate transporter 1(GLT-1);
learning and memory;
rat
- From:
Chinese Journal of Neuroanatomy
2025;41(4):452-460
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the effects of adenosine on learning and memory in rats thromboembolic stroke(TS)and its mechanism based on PI3K/Akt/CREB signaling pathway.Methods:36 male SD rats were randomly di-vided into sham group(Sham),TS group,TS+adenosine(TS+Ade)group and TS+adenosine+Akt inhibitor(TS+Ade+MK-2206)group.Preparation of rat TS model used autologous thrombus intravascular formation method.Mor-ris water maze(MWM)test was used to observe the learning and memory ability of rats.The morphological changes of hippocampal neurons were observed by Nissl staining.The expression of glutamate transporter 1(GLT-1)and glial fi-brillary acidic protein(GFAP)in CA1 region was determined by immunofluorescence.The protein expressions of PI3K,p-PI3K,Akt,p-Akt,CREB and p-CREB were determined by Western blot.Results:Through the rat TS mod-el,adenosine was able to improve the learning and memory ability,improve the hippocampal neuron cell morphological abpormality and vacuolation,nucleolar condensation and other phenomena in rats.Immunofluorescence results showed that GLT-1 and GFAP were co-localized,and adenosine could significantly enhance the fluorescence intensity of GFAP and GLT-1.Western blot results showed that adenosine can enhance the expression of p-PI3K,p-Akt,and p-CREB proteins,but the use of Akt inhibitors can to some extent inhibit the phosphorylation of PI3K,Akt,and CREB.Conclusion:Adenosine may enhance the expression of GLT-1 in astrocytes and increase the clearance of glutamate through activation of PI3K/Akt/CREB signaling pathway,thereby reducing the excitotoxicity and improving recognition and memory function.However,this effect is partially blocked by Akt inhibitors.
