Effects of regular aerobic exercise on NLRP3/caspase-1/GSDMD axis and learning-memory function in rats with middle cerebral artery occlusion
10.3969/j.issn.1001-1242.2024.09.001
- VernacularTitle:规律性有氧运动对大脑中动脉栓塞大鼠NLRP3/caspase-1/GSDMD轴及学习记忆功能的影响
- Author:
Jing CHENG
1
;
Yihan YANG
;
Yanping LIU
Author Information
1. 福建中医药大学,福建省福州市,350122
- Keywords:
aerobic exercise;
learning and memory;
microglia pyroptosis;
ischemic cerebral injury;
neuroinflammation
- From:
Chinese Journal of Rehabilitation Medicine
2024;39(9):1241-1249
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the possible mechanism of regular aerobic exercise in improving the leaming and memo-ry function in rats with middle cerebral artery occlusion reperfusion(MCAO/R). Method:Total of 36 SD rats were randomly divided into 3 groups:sham operation group(IS group),aero-bic exercise group(AE group),and model group(IC group).MCAO/R models were established in the IC and AE groups,while the IS group underwent the same arterial dissection without occlusion.After model estab-lishment,the rats in the AE group were trained on a treadmill for 14 days,while the rats in the IS group and IC group were only placed on the treadmill for the same duration without running.The neurological func-tion of the rats in each group was scored,the cerebral infarction focus of the rats was observed by magnetic resonance imaging T2WI scanning before and after the intervention,and the recognition and memory ability of the rats was detected by the new object recognition experiment before and after the intervention.The Western Blot was used to detect the expression of NLRP3,caspase-1,and GSDMD in the hippocampus,and immuno-histochemistry was used to detect the activation of microglia in the CA1 region of the ischemic hippocampus.The levels of IL-1β and IL-18 were detected by ELISA.The expression and co-localization of IBA1 with NL-RP3,caspase-1,and GSDMD were detected by immunofluorescence co-labeling assay. Result:Before intervention,the neurological function score and the signal intensity of the left cerebral cortex hippocampus of the IC Group were significantly higher than that of the IS group(P＜0.05),and the resolu-tion of new objects decreased significantly(P＜0.05).There were no significant differences between the AE and IC groups in the proportion of neurological deficit,cerebral infarction volume and novel object recogni-tion rate(P＞0.05).After 14 days of treadmill training intervention,compared with IC group,the AE group showed significantly lower neurological function scores(P＜0.05),reduced the percentage of cerebral infarction volume(P＜0.05),improved object recognition ability(P＜0.05),improved pathology in hippocampal CA1 area,reduced microglia activation level(P＜0.05),decreased levels of IL-1β and IL-18(P＜0.05),and significantly re-duced expression of NLRP3,caspase-1 and GSDMD proteins(P＜0.05).In addition,compared with the IC group,the accumulative optical density of NLRP3,GSDMD in CA1 and caspase-1 in CA3 regions of the ischemic hippocampus in the AE group was significantly decreased,and the number of IB A1 and NLRP3,IBA1 and GSDMD double-positive cells was significantly decreased(P＜0.05). Conclusion:Regular aerobic exercise can improve the ability of recognition and memory in MCAO/R rats,which may be related to the inhibition of hippocampal microglia pyroptosis and activation.
