Impacts of carnosic acid on learning and cognitive function in epileptic rats by regulating PKA-CREB signaling pathway
10.3969/j.issn.1000-484X.2025.06.022
- VernacularTitle:鼠尾草酸调节PKA-CREB信号通路对癫痫大鼠学习认知功能的影响
- Author:
Xiaoyan LIANG
1
;
Haimin WANG
;
Biao GENG
;
Ruixue MAN
;
Guangwei REN
Author Information
1. 山东第一医科大学第二附属医院药学部,泰安 271000
- Publication Type:Journal Article
- Keywords:
Carnosic acid;
Epilepsy;
Protein kinase A;
cAMP response element-binding protein;
Learning and cognitive function
- From:
Chinese Journal of Immunology
2025;41(6):1388-1393
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the impacts of carnosic acid(CA)on learning and cognitive function in epileptic rats and the mechanism of regulating PKA-CREB signaling pathway in this process.Methods:Epilepsy rat models were prepared by intraperi-toneal injection of 50 mg/kg PTZ.After successful modeling,the rats were randomly grouped into control group,model group,CA low-dose group,CA high-dose group,CA high+PKA inhibitor group(CA high+H-89 group),with 15 rats in each group.The epileptic be-havior of rats in each group was evaluated;Morris water maze experiment was applied to test the cognitive ability of rats;HE staining and Nissl staining were applied to detect the morphology of hippocampal tissue and neurons of rats in each group;ELISA was applied to detect the contents of IL-1β,TNF-α,MDA,and the SOD activity in the hippocampus of rats in each group;and Western blot was applied to detect the protein expressions of PKA,p-PKA,CREB,p-CREB and BDNF in the hippocampus of rats in each group.Results:Compared with control group,the hippocampal neurons of rats in model group were irregularly arranged,with pyknosis of the nuclei,and the number of neurons decreased,the epilepsy frequency,Racine grading,escape latency,time of first platform crossing,and levels of IL-1β,TNF-α and MDA all increased,the frequency of crossing the platform,SOD activity,p-PKA/PKA,p-CREB/CREB,and the expression of BDNF protein all reduced(P<0.05);compared with model group,the arrangement of neuronal cells in hippocampal tissue of rats in CA group gradually became orderly,nuclear pyknosis gradually decreased,and the number of neurons increased,the epilepsy frequency,Racine grading,escape latency,time of first platform crossing,and levels of IL-1β,TNF-α and MDA all reduced,the frequency of crossing the platform,SOD activity,p-PKA/PKA,p-CREB/CREB,and the expression of BDNF protein all increased(P<0.05);further injection of PKA inhibitors on the basis of high-dose CA treatment showed that the improvement effects of high-dose CA on cognitive dysfunction,neuronal damage,inflammation,and oxidative stress in epileptic rats were reversed(P<0.05).Conclusion:CA can improve the learning and cognitive function of epileptic rats by activating the PKA-CREB signaling pathway.
