Effect of Wenyang， Jieyu， and Wenyang Jieyu Prescriptions on Hippocampal Microglia of Mice with Depression-Like Behavior Induced by Secondary LPS Exposure / 中国实验方剂学杂志

ABSTRACT

Objective:To observe the activation of microglia and the expression of inflammatory factors in hippocampus of mice with depression-like behavior after mother-infant separation （MS） combined with lipopolysaccharide （LPS） stress， and to explore the possible anti-depression mechanisms of Wenyang （WY）， Jieyu （JY）， and Wenyang Jieyu （WYJY） prescriptions from the perspective of warming Yang and relieving depression. Method:Seventy offspring mice were randomly divided into a normal group （<italic>n</italic>=10）， a LPS stress group （<italic>n</italic>=10）， and a modeling group （<italic>n</italic>=50）. After undergoing 8 h·d^-1mother-infant separation during postnatal day 5 （PD₅）–PD₁₄， mice in the modeling group were further divided into the MS + LPS group， WY group， JY group， WYJY group， and fluoxetine （FLU） group， with 10 in each group. The birth date of the offspring mice was recorded as PD₀. The mice in the normal， LPS， and MS + LPS groups were fed a normal diet during PD₂₁–PD₉₀， while those in the other groups were treated with the mixtures of corresponding drugs and feed， followed by seven-day intraperitoneal injection of LPS since PD₉₁ for inducing depression. The depression-like behavior of mice in each group was detected in the open-field， O-maze， and social interaction tests. The protein expression of microglia-specific ionized calcium-binding adaptor molecule 1 （Iba-1） in the hippocampus was assayed by immunohistochemistry， and the mRNA expression of interleukin-1<italic>β </italic>（IL-1<italic>β</italic>）， interleukin-6 （IL-6）， tumor necrosis factor-<italic>α </italic>（TNF-<italic>α</italic>）， Iba-1， and glucocorticoid receptor （GR） by real-time fluorescence quantitative PCR （Real-time PCR）. Result:Compared with the normal group， the LPS group exhibited significantly reduced residence time at the central area within 5 min （<italic>P</italic><0.01） and shortened total exercise distance （<italic>P</italic><0.01）. In the MS + LPS group， the open-arm activity time and the total activity distance decreased significantly （<italic>P</italic><0.01， <italic>P</italic><0.05）， whereas the training， discrimination and exploration time increased significantly （<italic>P</italic><0.01）. The expression of Iba-1 in hippocampal CA1 region of mice in the LPS and MS + LPS groups was remarkably elevated （<italic>P</italic><0.01）. Compared with the LPS group， the MS + LPS group displayed significantly prolonged distance of 5-min exercise （<italic>P</italic><0.05）， increased training， discrimination and exploration time （<italic>P</italic><0.05， <italic>P</italic><0.01）， and up-regulated Iba-1 expression in hippocampal CA1 area （<italic>P</italic><0.01）. As revealed by comparison with the MS + LPS group， both the total 5-min exercise distance （<italic>P</italic><0.01） and the training and discrimination time （<italic>P</italic><0.01， <italic>P</italic><0.05） of mice in each administration group was significantly shortened. The discrimination and exploration time of mice in the JY， WYJY， and FLU groups was significantly reduced （<italic>P</italic><0.01）， and the expression of Iba-1 in hippocampal CA1 region of mice in each administration group was significantly down-regulated （<italic>P</italic><0.01）. Conclusion:The warming Yang and relieving depression method helps to inhibit the occurrence and development of depression due to its efficacy in activating microglia in hippocampus of depression mice and lowering the expression of IL-1<italic>β</italic>， IL-6， and TNF-<italic>α</italic>.