Mechanistic study on the improvement of aerobic exercise on Alzheimer's disease in rats based on tran-scriptomics and metabolomics
10.3969/j.issn.1001-1242.2025.08.001
- VernacularTitle:基于转录组学与代谢组学的有氧运动改善大鼠阿尔茨海默病作用机制研究
- Author:
Chunxiao WANG
1
;
Yuan YAO
1
;
Li LI
1
Author Information
1. 哈尔滨体育学院,黑龙江省哈尔滨市,150006
- Publication Type:Journal Article
- Keywords:
aerobic exercise;
transcriptomics;
metabolomics;
Alzheimer's disease;
mechanism
- From:
Chinese Journal of Rehabilitation Medicine
2025;40(8):1129-1136
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the targets and mechanisms of aerobic exercise on Alzheimer's disease(AD).Method:Thirty-two male clean-grade Wistar rats were randomly assigned to one of four groups:control,mod-el,positive drug and aerobic exercise.After intervention,the Morris water maze was employed to assess the learning and memory capabilities of the rats,and hematoxylin and eosin staining was utilized to observe patho-logical changes in hippocampal tissue.Transcriptomic and metabolomic analyses were conducted to identify dif-ferential metabolites and key genes associated with disease progression,with a focus on the expression of key genes through integrated analysis.Result:The water maze experiment showed that the aerobic exercise group significantly improved the learning and cognitive abilities of D-galactose-induced Alzheimer's disease model rats.Pathological staining showed a de-crease in the number of cells in the hippocampal CA1 region of the model group rats,characterized by deep staining of the nucleus and cytoplasm,cell shrinkage,loose and disordered arrangement,blurred boundaries be-tween the nucleus and cytoplasm,and increased gaps.The cell structure of hippocampal neurons in the aero-bic exercise group of rats was relatively clear and tends to be complete,with a decreasing trend in intercellu-lar gaps.No large-scale neuronal shrinkage was observed in the field of view,and the cell volume appeared normal.Transcriptomics screened out key genes mainly including four genes:indoleamine 2,3-dioxygenase 1(IDO1),tryptophan 2,3-dioxygenase 2(TDO2),plexin B1(PLXNB1),and tripartite motif protein 11(TRIM 11).Metabolomics screening identified ten differential metabolites,including N-formylcarnitine,trypto-phan,Kynurenine,5-hydroxytryptamine,5-hydroxytryptophan,creatine,N-acetylaspartate glutamate,histidine,Hydroxyprolyl-Isoleucine,and pyridoxine.This study showed that aerobic exercise significantly improved the learning and memory abilities of D-galactose-induced AD model rats,alleviated the damage and reduction of hippocampal CA1 neurons.Integrated analysis found that the content of tryptophan,kynurenine,5-hydroxytryp-tamine,and 5-hydroxytryptophan was directly regulated by IDO1 and TDO2.Conclusion:IDO1 and TDO2 are important targets for aerobic exercise in the treatment of AD.The neuropro-tective effects and reduction of oxidative stress and inflammation are the key therapeutic mechanisms of aero-bic exercise in AD.
