Physical exercise ameliorates cognitive impairment in Alzheimer's disease by up-regulating α/β-hydrolase domain-containing 12 in microglia
10.3969/j.issn.1001-1242.2025.10.001
- VernacularTitle:运动训练上调小胶质细胞α/β-水解酶结构域12改善阿尔茨海默病小鼠认知功能的作用与机制研究
- Author:
Handie CHEN
1
;
Shiyin LI
;
Lili LI
Author Information
1. 广州中医药大学,广州市,510000
- Publication Type:Journal Article
- Keywords:
Alzheimer's disease;
physical exercise;
cognitive impairment;
microglia;
α/β-hydrolase domain-containing 12
- From:
Chinese Journal of Rehabilitation Medicine
2025;40(10):1449-1458
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To investigate the protective mechanism of physical exercise in regulating the transition of microgli-al phenotype and cognitive impairment in Alzheimer's disease(AD).Method:Male 5xFAD mice at the age of 5 months were randomly divided into physical exercise(PE)and control group,and 5-month-old male C57BL/6J mice were taken as wild type group.Three months of wheel-running exercise was conducted in PE group.After completion of exercise program,the anxiety-like behavior and cognitive impairment were assessed by Morris water maze test and open field test.The protein expression of α/β-hydrolase domain-containing 12(ABHD12)was detected by Western Blots.The cellular location of AB-HD12 was detected by immunofluorescence staining.In vitro study,BV-2 cells were transfected with lentivirus overexpression or knockdown ABHD12.Aβ-42 oligomer was incubated to establish the AD model in vitro.RT-qPCR、western blots and immunofluorescence staining were performed to verify the up-and down-regulation of ABHD12,as well as to explore the effect of ABHD12 in the transition of microglial phenotype.Result:Physical exercise ameliorated the cognitive and emotional dysfunction in 5xFAD mice.Physical exer-cise also reduced Aβ deposition and maintained the synaptic plasticity.Mechanically,physical exercise up-regu-lated the expression of ABHD12,which is expressed in microglia,but not in astrocytes or neurons.Physical exercise also increased the number of M2 microglia and decreased the number of M1 microglia.The knock-down of ABHD12 exacerbates the inflammatory response of Aβ oligomer induced BV-2 cells.Conclusion:Physical exercise ameliorated cognitive dysfunction in Alzheimer's disease by up-regulating AB-HD12,prompting the transition of microglial phenotype to inhibit the inflammation,and to reduce the Aβ de-position.
