Study on the attenuation of depression-like behaviors in chronic copper-exposed mice by Ginkgo biloba extract through the proBDNF/mBDNF balance
10.16557/j.cnki.1000-7547.2025.03.004
- VernacularTitle:银杏叶提取物通过proBDNF/mBDNF平衡改善慢性铜暴露小鼠抑郁样行为
- Author:
Zhihua JIANG
1
;
Caixing DAI
;
Xinyue ZHANG
;
Wenping ZHANG
;
Jianguo LI
Author Information
1. 山西医科大学医学科学院,太原 030001;山西医科大学生理学系,太原 030001;山西医科大学细胞生理学教育部重点实验室,太原 030001
- Publication Type:Journal Article
- Keywords:
copper exposure;
depression;
ginkgo biloba extract(EGb);
brain-derived neurotrophic factor(BD-NF);
hippocampus;
mouse
- From:
Chinese Journal of Neuroanatomy
2025;41(3):289-297
- CountryChina
- Language:Chinese
-
Abstract:
Objective:To explore the mechanism through which the Ginkgo biloba extract(EGb)ameliorates depres-sion-like behaviors in chronic copper-exposed mice.Methods:A mouse model with depression was induced by chronic oral administration of copper sulfate solution(200 mg/L),followed by oral administration of the EGb(120 mg/L)for one month.Elevated plus-maze test,forced swimming test,and sucrose preference test were employed to detect the de-pression-like behaviors of mice.TUNEL staining was utilized to examine apoptosis in the hippocampal region of mice.Immunohistochemistry was adopted to detect the in situ expression of pro-brain-derived neurotrophic factor(proBDNF)and brain-derived neurotrophic factor(BDNF)in the hippocampal region.RT-qPCR was used to measure the expression of the BDNF mRNA.Western blot was utilized to determine the expressions of proteins such as proBDNF,mature BDNF(mBDNF),cAMP response element binding protein(CREB),phospho-CREB(p-CREB),tyrosine kinase receptor B(TrkB),p75 neurotrophin Receptor(p75NTR),furin,proprotein convertase subtilisin/kexin type 1(PCSK1),and matrix metalloproteinase-9(MMP9).Results:Chronic copper exposure led to depression-like behaviors in mice,in-creased neuronal apoptosis in the hippocampal region,enhanced proBDNF expression and reduced mBDNF expression(P＜0.05),decreased the expression of the downstream receptor protein TrkB and increased the expression of p75NTR(P＜0.05),and decreased the level of CREB and p-CREB(P＜0.05).Meanwhile,the expressions of intracellular proteases furin and PCSK1 in the hippocampal region of mice with depression-like behaviors decreased(P＜0.05),while the expression of extracellular protease MMP9 increased(P＜0.05).EGb was capable of alleviating depression-like behaviors and neuronal apoptosis in mice and partially reversing the abnormal expressions of BDNF,proBDNF,TrkB,p75NTR,CREB,p-CREB,furin,and PCSK1 proteins caused by copper exposure.Conclusion:Chronic copper exposure can lead to depression-like behaviors and apoptosis in mice.EGb can reverse these manifestations and corre-late with the balance of proBDNF/BDNF in the hippocampal region,which may offer novel insights for the treatment of depression.
