Suanzaoren Tang Regulates SP1/SK1/S1PR1 Signaling Pathway to Reduce Hippocampal Neuroinflammation and Improve Synaptic Plasticity in Rat Model of Depression
10.13422/j.cnki.syfjx.20251707
- VernacularTitle:酸枣仁汤调控SP1/SK1/S1PR1信号通路改善抑郁模型大鼠海马神经炎症和突触可塑性的作用机制
- Author:
Jianyu FENG
1
;
Wenhua WANG
1
;
Youwen WANG
1
;
Ying TAN
1
;
Xusheng TIAN
2
Author Information
1. Graduate School， Heilongjiang University of Chinese Medicine， Harbin 150040， China
2. The First Clinical Medical College， Heilongjiang University of Chinese Medicine， Harbin 150040， China
- Publication Type:Journal Article
- Keywords:
family with sequence similarity 19， member A5 （FAM19A5）;
depression;
specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway;
synaptic plasticity;
neuroinflammation
- From:
Chinese Journal of Experimental Traditional Medical Formulae
2025;31(21):1-10
- CountryChina
- Language:Chinese
-
Abstract:
ObjectiveTo evaluate the effect of Suanzaoren Tang on the rat model of depression established by solitary culture combined with chronic unpredictable mild stress by reshaping the inflammatory microenvironment and mediating changes in hippocampal synaptic plasticity. MethodsSeventy-two male SD rats were randomized by a random number table into six groups： control group， model group， fluoxetine group （0.003 6 g·kg-1）， and high-（10 g·kg-1）， medium-（5 g·kg-1）， low-dose （2.5 g·kg-1）Suanzaoren Tang groups， with 12 rats per group. The sucrose preference rate and open field test scores of rats in each group were observed. Western blot was employed to determine the expression levels of the key proteins in the specificity protein 1 （SP1）/sphingosine kinase 1 （SK1）/sphingosine-1-phosphate receptor 1 （S1PR1） signaling pathway， as well as hippocampal proteins synaptophysin Ⅰ （SYNⅠ）， postsynaptic density protein-95 （PSD-95）， and family with sequence similarity 19， member A5 （FAM19A5）. Immunohistochemistry was employed to detect the positive expression of SP1， PSD-95， SYNⅠ， interleukin （IL）-10， and IL-6. Real-time fluorescence quantitative polymerase chain reaction （Real-time PCR） was employed to determine the mRNA levels of SP1 and S1PR1. Finally， transmission electron microscopy was employed to observe the ultrastructural changes of hippocampal synapses. ResultsCompared with the control group， the model group exhibited a decrease in sucrose preference index （P<0.01） and reduced total scores for horizontal and vertical movements in the open field test （P<0.01）， which indicated the successful modeling of depression. Moreover， the model group showed reduced synaptic vesicles in the hippocampus （P<0.01）， up-regulated expression of SP1， SK1， S1PR1， and IL-6 （P<0.01）， and down-regulated expression of SYNⅠ， PSD-95， FAM19A5， and IL-10 （P<0.01）. Compared with the model group， high- and medium-dose Suanzaoren Tang and fluoxetine increased the sucrose preference index and the total scores for horizontal and vertical movements in the open field test （P<0.01）. All Suanzaoren Tang groups and the fluoxetine group demonstrated reductions in SP1， SK1， S1PR1， and IL-6 expression （P<0.05， P<0.01）， alongside restored synaptic vesicles in the hippocampus （P<0.05， P<0.01）. ConclusionSuanzaoren Tang modulates hippocampal expression of FAM19A5， SYNⅠ， PSD-95， IL-10， IL-6， and the SP1/SK1/S1PR1 pathway in the rat model of depression. The antidepressant effects may be related to the ability of reducing neuroinflammation and enhancing synaptic plasticity.
