Syndromes and Mechanisms of Depression Induced by Second Hit in Mice
10.13422/j.cnki.syfjx.20232244
- VernacularTitle:二次打击致抑郁小鼠的证候属性及其机制
- Author:
Zihan GONG
1
;
Ying WANG
2
;
Jingwen YANG
2
;
Wenqing LIANG
3
;
Danhua MENG
2
;
Kaijie SHE
2
;
Yuan LIANG
2
;
Guangxin YUE
2
Author Information
1. Ningxia Chinese Medicine Research Center， Yinchuan 750021， China
2. Institute of Basic Theory for Chinese Medicine， China Academy of Chinese Medical Sciences， Beijing 100700， China
3. Traditional Chinese Medicine （TCM） School， Henan University of Chinese Medicine， Zhengzhou 450046， China
- Publication Type:Journal Article
- Keywords:
second hit;
depression-like behavior;
5-hydroxytryptamine （5-HT） system;
hypothalamic-pituitary-adrenal （HPA） axis;
brain-derived neurotrophic factor （BDNF） signaling pathway;
Yang deficiency and liver depression
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2024;30(6):29-38
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the syndromes and mechanisms of depression induced by maternal separation （MS） combined with chronic restraint stress （RS） in mice. MethodOn postnatal day 0 （PD0）， the offspring mice were randomized into a blank group （NC） and a modeling group. The mouse model of depression was established by MS+RS for 21 days. After removal of female mice on PD21， the modeled mice were randomized into model， Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups， with 15 mice in each group. The sucrose preference， tail suspension， and open field tests were carried out to evaluate the anxiety and depression-like behavior in mice. Enzyme-linked immunosorbent assay was used to measure the adrenocorticotrophic hormone （ACTH） and corticosterone （CORT） levels in mouse plasma. High performance liquid chromatography-electrochemical detector was used to determine the content of monoamine neurotransmitters in the hippocampus. Real-time fluorescence quantitative polymerase chain reaction was employed to determine the mRNA levels of genes in the 5-hydroxytryptamine （5-HT） system， hypothalamic-pituitary-adrenal （HPA） axis， and brain-derived neurotrophic factor （BDNF） signaling pathway in the hippocampus. Immunohistochemistry was employed to determine the expression levels of proteins in the 5-HT system and HPA axis in the hippocampus. The Simple Western system was used to determine the protein levels of BDNF and tyrosine kinase receptor B （TrkB） in the hippocampus. ResultCompared with the NC group， the model group exhibited depression-like behavior， which was significantly relieved by Wenyang Jieyu prescription and fluoxetine. Compared with the NC group， the model group showed elevated levels of CORT and ACTH in the plasma （P<0.01）， which， however， were lowered by Wenyang Jieyu prescription and fluoxetine （P<0.05， P<0.01）. Compared with the NC group， the model group showed inhibited expression of neurotransmitters in the hippocampus （P<0.05， P<0.01）， while Wenyang Jieyu prescription and fluoxetine restored the expression of neurotransmitters （P<0.05， P<0.01）. Compared with NC group， the model group showed inhibition of the 5-HTergic nerve and abnormal activation of the HPA axis， and Wenyang Jieyu prescription and fluoxetine regulated the abnormal state of the 5-HTergic nerve and HPA axis. Compared with NC group， the modeling down-regulated the mRNA and protein levels of BDNF and TrkB in the hippocampus （P<0.05， P<0.01）， which， however， were recovered in Wenyang， Jieyu， Wenyang Jieyu， and fluoxetine groups （P<0.05， P<0.01）. ConclusionThe mouse model of depression induced by MS+RS may present the syndrome of Yang deficiency and liver depression. Wenyang Jieyu prescription may increase the content of hippocampal neurotransmitters by regulating the 5-HT system and the BDNF signaling pathway mediated by the HPA axis， thereby alleviating depression-like behavior in mice.
