Moderate-intensity interval aerobic training slows brain aging in rats by inhibiting the apoptosis pathway mediated by miR-21-3p
10.3969/j.issn.1000-6710.2024.12.005
- VernacularTitle:中等强度间歇有氧训练通过抑制miR-21-3p介导的凋亡途径减缓大鼠脑衰老
- Author:
Liting LV
1
;
Qiaojing GAO
;
Jinmei ZHANG
;
Renfan LIU
;
Lu WANG
Author Information
1. 成都体育学院运动医学与健康学院 成都 610041;四川省医学科学院,四川省人民医院(电子科技大学附属医院),医学遗传中心 成都 610072
- Publication Type:Journal Article
- Keywords:
moderate-intensity interval aerobic training;
aging;
miR-21-3p;
cell apoptosis;
learning and memory
- From:
Chinese Journal of Sports Medicine
2024;43(12):969-980
- CountryChina
- Language:Chinese
-
Abstract:
Objective To examine the impact of moderate-intensity intermittent aerobic training on the expression of microRNA-21-3p(miR-21-3p),so as to establish a theoretical foundation for under-standing the potential mechanisms of exercise interventions mitigating the decline in learning and memo-ry functions associated with brain aging. Methods Forty-five three-month specific pathogen-free(SPF) male Sprague-Dawley(SD) rats were randomly divided into a control group(group C),an aging group (group A),and an aging+exercise group(group AE),following a one-week acclimatization period. Group A and AE were administered intraperitoneal injections of D-galactose(D-gal) for six weeks,and the latter group underwent an eight-week regimen of moderate-intensity interval aerobic training. Behavioral assessments were conducted in all groups 24 hours after modeling. Nissl staining was used to detect the distribution of neurons,while in situ terminal transferase labeling(TUNEL) was employed to identify apoptosis in hippocampal cells. Moreover,small RNA sequencing was conducted to detect miRNA expression,while real-time quantitative polymerase chain reaction(qRT-PCR) was employed to measure the relative content of miR-21-3p. Meanwhile,the targeting relationship between miR-21-3p and tumor protein p53(p53) was confirmed using the dual luciferase reporter gene assay,while the ex-pression levels of p53,the B lymphoblastoma-2 protein family member X(Bax),and the B lympho-blastoma-2(Bcl-2) were measured using Western Blotting. Results ①The results of the Morris water maze positioning navigation experiment before and after the intervention showed that the overall swim-ming distance of rats in groups A and AE was significantly longer than group C(P<0.05,P<0.01),with that of group AE significantly shorter than group A(P<0.01,P<0.05). ② Nissl's staining re-vealed that,compared to group C,hippocampal neurons in group A exhibited disorganization,reduced staining intensity,indistinct nuclei from surrounding tissues,and a scarcity of Nissl bodies,while those of group AE were sparse,with fewer levels and significantly reduced numbers. However,com-pared with group A,the hippocampal neurons in group AE were arranged more neatly,with more lay-ers and more Nissl bodies. ③TUNEL results showed that the apoptosis rate of hippocampal cells in group A and AE was significantly higher than group C(P<0.01,P<0.05),with that of group AE signif-icantly lower than group A(P<0.01). ④ Small RNA sequencing results showed that the expression of plasma exosomes miR-21-3p in group A and AE was significantly higher than group C(P<0.01,P<0.05),with that of group AE significantly lower than group A(P<0.01). ⑤According to the results of qRT-PCR,the expression of miR-21-3p in group A and AE was significantly higher than group C(P<0.01),with that of group AE significantly lower than group A(P<0.05). ⑥Luciferase experiment showed that miR-21-3p had a targeted relationship with p53. Compared with Vector mimics+pcD-NA3.1-p53,miR-21-3p mimics and pcDNA3.1-p53 co-transfected HEK293T cells could significantly improve p53 luciferase activity. ⑦According to Western Blotting results,the protein expressions of p53 and Bax and the ratio of Bax/Bcl2 in group A and AE were significantly higher than group C(P<0.01,P<0.05),but that of Bcl-2 was significantly lower than the latter group(P<0.01). Moreover,the expression of p53 and Bax protein and the ratio of Bax/Bcl-2 in group AE were significantly low-er than group A(P<0.05,P<0.01),but that of Bcl-2 protein was significantly higher than group A(P<0.01). Conclusions It is suggested that 8-week moderate intensity intermittent aerobic training may down-regulate miR-21-3p mediated by peripheral blood exosomes,reduce the expression of miR-21-3p in brain tissue,target miR-21-3p to bind p53,and reduce the occurrence of apoptosis,thus im-proving the learning and memory ability of rats.
