Aerobic Exercise-Induced Hippocampal Exosomal miR-126a-5p in Ameliorating Diabetic Cognitive Dysfunction
10.13865/j.cnki.cjbmb.2025.06.1058
- VernacularTitle:中等强度运动诱导海马外泌体miR-126a-5p改善2型糖尿病小鼠认知功能障碍
- Author:
Si-Jie LAI
1
;
Yi-Xiao MA
;
Jian-Ting SUN
;
Zheng-Hong KANG
;
Hua LIU
Author Information
1. 武汉体育学院研究生院,武汉 430079
- Publication Type:Journal Article
- Keywords:
aerobic exercise;
diabetes mellitus type 2(T2DM);
miR-126a-5p;
exosomes;
inflamma-tion;
hippocampal tissue
- From:
Chinese Journal of Biochemistry and Molecular Biology
2025;41(9):1320-1331
- CountryChina
- Language:Chinese
-
Abstract:
Diabetes-related cognitive impairment(DCI)is a major complication of type 2 diabetes melli-tus(T2DM).Although exercise is essential in alleviating DCI,the underlying mechanisms remain un-clear.The aim of this study is to investigate the role and mechanism of exosomal miR-126a-5p induced by exercise in ameliorating DCI.Twenty-four 16-week-old male db/db mice were randomly divided into dia-betes group(n=12;DM)and exercise intervention group(n=12;DE).The control group consisted of male m/m mice of the same age group(n=12;CON).The DE group underwent 8 weeks of moderate in-tensity treadmill training(10 m/min,5 days a week).In the MWM experiment,compared to the CON group,the DM group exhibited prolonged escape latency(P<0.01),reduced swimming speed and target quadrant time(P<0.001),and decreased expression of miR-126a-5p and EX-miR-126a-5p in hipp-ocampal tissue(P<0.001).After exercise intervention,the DE group showed improved performance with decreased escape latency(P<0.05),increased swimming speed and target quadrant time(P<0.05),and elevated levels of exosomal miR-126a-5p(P<0.001).Morphological staining revealed a de-crease in the expression and proportion of NeuN in hippocampal neurons and an increase in the expression and proportion of glial cells in the CA1 and CA3 regions of DM group mice compared to CON group mice(P<0.05),while DE group mice showed increased fluorescence intensity and proportion of neurons(P<0.05).Western blotting analysis revealed that the DM group also showed significant upregulation of amy-loid β(Aβ),high mobility group box 1(Hmgb1),and NF-κB in the hippocampus(P<0.05),which were reduced after exercise(P<0.05).Moreover,exosomal miR-126a-5p overexpression greatly de-creased the levels of Hmgb1,NF-κB,and amyloid precursor protein(APP)in HT22 cells and TNF-α,IL-1β in supernatant exposed to HG(P<0.05),while inhibition of miR-126a-5p led to increased levels of these proteins(P<0.05).In conclusion,eight weeks of treadmill exercise improved cognitive function in db/db mice,likely through the EXs-miR-126/HMGB1/NF-κB pathway to reduce inflammation in hip-pocampal tissue.
