Mechanism of Wenyang Jieyu Prescription in Regulating Activation of Mouse Hippocampal Microglia Based on JAK2/STAT3 Signaling Pathway
10.13422/j.cnki.syfjx.20241640
- VernacularTitle:基于JAK2/STAT3信号通路探讨温阳解郁方调节小鼠海马小胶质细胞激活的机制
- Author:
Ying WANG
1
;
Zihan GONG
2
;
Wenqing LIANG
3
;
Jingwen YANG
4
;
Guangxin YUE
1
Author Information
1. Institute of Basic Theory for Chinese Medicine， China Academy of Chinese Medical Sciences，Beijing 100700， China
2. Ningxia Chinese Medicine Research Center，Ningxia 750000， China
3. Hengshanqiao People's Hospital in Changzhou Economic Development Zone， Changzhou 213161， China
4. Institute of Basic Research in Clinical Medicine， China Academy of Chinese Medical Sciences，Beijing 100700， China
- Publication Type:Journal Article
- Keywords:
maternal-infant separation;
depression-like behavior;
microglia;
Janus kinase 2 （JAK2）/signal transducer and activator of transcription 3 （STAT3） pathway;
Wenyang Jieyu prescription
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(8):88-96
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo explore the mechanism of the Wenyang Jieyu prescription in regulating depression-like behavior in mice after maternal-infant separation combined with secondary stress. MethodsAfter birth， the rats were randomly divided into blank （NC） group， maternal-infant separation （MS） group， restraint stress （RS） group， maternal-infant separation combined with restraint stress （MRS） group， Wenyang group， Jieyu group， Wenyang Jieyu （XSF） group， and minocycline group. Maternal-infant separation was performed on day 5 （PD5）， followed by weaning at PD21 and prophylactic administration. The dose of Wenyang group， Xiaoyao group， XSF group and minocycline group were 5.85， 12.03， 16.71 g·kg-1 and 50 mg·kg-1， respectively. Restraint stress was applied on PD90. The model was evaluated using glucose， social interaction， open field， and O-maze behavior tests， as well as high-performance liquid chromatography to measure serotonin， dopamine， and other neurotransmitters. The expression level of ionized calcium-binding adaptor molecule-1 （Iba-1） protein， a marker of hippocampal microglia， was detected by immunohistochemistry. Protein expression levels of Janus kinase 2 （JAK2） and signal transducer and activator of transcription 3 （STAT3） in the hippocampus were analyzed by an automatic protein expression analysis system. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was used to detect mRNA expression levels of M1 markers， JAK2/STAT3 pathway-related genes， and cytokines in hippocampal microglia in each group. ResultsCompared with the NC group， the MRS group exhibited depression-like behavior， with significantly decreased levels of neurotransmitters in the hippocampus （P<0.05， P<0.01）， increased expression of Iba-1 （P<0.01）， and elevated protein levels of JAK2 and STAT3 （P<0.05）. The mRNA expression levels of CD68， CD11b， IL-1β， JAK2， and STAT3 were significantly increased （P<0.01）， while IL-10 mRNA expression was significantly decreased （P<0.01）. Compared with the MRS group， the XSF and minocycline groups showed some improvement in depression-like behavior. In these groups， the hippocampal neurotransmitter content was significantly increased （P<0.05， P<0.01）， and Iba-1 expression was significantly decreased （P<0.01）. The protein levels of JAK2 and STAT3 in the XSF group showed a downward trend. The mRNA expression levels of CD68， CD11b， JAK2， STAT3， and IL-1β in the hippocampus were significantly decreased in the XSF and minocycline groups （P<0.05， P<0.01）， while IL-10 mRNA expression was significantly increased （P<0.05， P<0.01）. ConclusionWenyang Jieyu prescription can regulate depression-like behavior in maternal-infant separation mice combined with secondary stress by inhibiting the polarization of hippocampal microglia to the M1 phenotype. The regulation of hippocampal microglia polarization by Wenyang Jieyu prescription may be associated with the JAK2/STAT3 pathway.
