Effects of carnosine on hippocampal Akt/mTOR pathway and autophagy in rats with vascular cognitive impairment
10.16557/j.cnki.1000-7547.2024.06.007
- VernacularTitle:肌肽对血管性认知功能障碍大鼠海马内Akt/mTOR通路及自噬的影响
- Author:
Gao WANG
1
;
Jinying LU
1
;
Ruili RAN
1
;
Xinmin ZHAO
1
;
Jiang BIAN
1
;
Yutong WANG
1
;
Xiaohan JIANG
1
;
Jing YANG
1
Author Information
1. 锦州医科大学基础医学院生物化学与分子生物学教研室,锦州 121001
- Publication Type:Journal Article
- Keywords:
carnosine(CAR);
vascular cognitive impairment(VCI);
autophagy;
Akt/mTOR signaling pathway;
oxidative stress;
rat
- From:
Chinese Journal of Neuroanatomy
2024;40(6):713-723
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the effects of carnosine(CAR)on the spatial learning and memory abilities of rats with vascular cognitive impairment(VCI),and to explore the roles of the Akt/mTOR pathway and autophagy in this process.Methods:Fifty male Sprague-Dawley(SD)rats were randomly divided into sham-operated(Sham)group,VCI group,VCI+CAR-L group,VCI+CAR-M group,and VCI+CAR-H group.The spatial learning and memory abilities of rats were evaluated by the Morris water maze experiment;Nissl staining was used to detect the damage in the hippocampal CA1 region;the nitroblue tetrazolium and thiobarbituric acid methods were used to measure the activities of superoxide dismutase(SOD)and malondialdehyde(MDA)content in hippocampal tissue;Western Blot was performed to determine the expression of p-Akt,p-mTOR,Beclin-1,and LC3B proteins,and immunofluorescent staining was con-ducted to detect changes in LC3B expression in the CA1 region.SH-SY5Y cells were divided into control group,oxy-gen-glucose deprivation/reperfusion(OGD/R)group,OGD/R+rapamycin(RAPA),OGD/R+CAR(1.2 mmol/L)group,and OGD/R+CAR+RAPA group.Methyl thiazolyl tetrazolium assay was used to detect neuronal survival rate;Western Blot was used to detect the levels of p-mTOR,Beclin-1,and LC3B in neuronal cells;immunofluorescent stai-ning was performed to assess the degree of autophagy.Results:CAR could improve the learning and memory abilities of VCI rats,reduce hippocampal tissue cell damage,and inhibit oxidative stress(P＜0.01).CAR increased the expres-sion of p-Akt,p-mTOR,and p62 proteins(P＜0.01 or P＜0.05)and decreased the expression of Beclin-1 and the ra-tio of LC3B Ⅱ/Ⅰ(P＜0.01 or P＜0.05).CAR significantly increased the survival rate of SH-SY5Y cells after OGD/R(P＜0.01)and inhibited autophagy in hippocampal neurons.Furthermore,the intervention with RAPA counteracted the therapeutic effect of CAR,reduced the survival rate of SH-SY5Y groups(P＜0.01),and enhanced autophagy.Conclusion:CAR can improve rat VCI injury,and its mechanism may involve inhibiting oxidative stress,activating the Akt/mTOR signaling pathway in neuronal cells,and thereby inhibiting excessive autophagy to exert a protective effect.
