BACKGROUND:In recent years,with the rapid development of biomedicine,the study of brain aging and exosomes has attracted more and more attention,but there is no bibliometrics analysis in this field. OBJECTIVE:To objectively analyze domestic and foreign literature on brain aging and exosomes in the past 15 years,to summarize the research status,hot spots,and development trends in this field. METHODS:Using the core database of Web of Science as a search platform,we downloaded the literature on brain aging and exosomes published from the establishment of the database to December 28,2022,and analyzed the data from the aspects of country or region,institution,author,keywords,and co-cited literature using CiteSpace 6.1.R6 visualization software. RESULTS AND CONCLUSION:A total of 1 045 research articles were included,and the number of publications on brain aging and exosomes research both domestically and internationally was showing an increasing trend year by year.The United States ranked first with 429 papers,and China ranked second with 277 papers.Louisiana State University ranked first with 16 articles.Professor Lukiw Walter J from Louisiana State University in the United States was the author with the highest number of publications,and Professor Bartel DP from the Massachusetts Institute of Technology was the author with the most citations.The most prolific Journal was the International Journal of Molecular Sciences.Alzheimer's disease,microRNA,gene expression,extracellular vesicles,exosomes,oxidative stress,and biomarkers are the most relevant terms.According to the research on hot topics,biomarkers have become a new research hotspot.The above results indicate that the research on brain aging and exosomes has gradually increased in the past 15 years.The research direction has gradually shifted from the initial exploration of the expression of miRNAs in central nervous system diseases related to brain aging to the search for biomarkers that can identify and diagnose neurodegenerative diseases.The study of exocrine miRNAs to protect central nervous system from damage has emerged as promising therapeutic strategy.

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.

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.