CRHR1 antagonist alleviates LPS-induced depression-like behaviour in mice

CRHR1 拮抗剂可减轻小鼠 LPS 诱发的抑郁样行为

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作者:Jie Sun, Lili Qiu, Hui Zhang, Zhiqiang Zhou, Lingsha Ju #, Jiaojiao Yang #

Background

Maladaptation of the HPA (hypothalamic-pituitary-adrenal) axis plays an important role in depression-like behaviour, but the specific molecular mechanisms are unknown. Here, we determined the roles of CRHR1 (corticotrophin releasing hormone receptor 1) and nectin3 in LPS (lipopolysaccharide)-induced depression-like behaviour in mice.

Conclusion

CRHR1antagonist showed antidepressant effects in LPS-induced depressive mice, and CRHR1/nectin3 signalling may play a crucial role in this process.

Methods

C57BL/6 male mice were intraperitoneally injected with LPS (0.83 g/kg), and the open field, novelty-suppressed feeding, forced swimming, and tail suspension tests were performed after intraperitoneal injections of saline or antalarmin (20 mg/kg). The hippocampal mRNA levels of CRHR1 and nectin3 were determined by quantitative reverse transcription-PCR. The hippocampal protein levels of CRHR1, nectin3, and calbindin were measured by western blotting. The CORT (corticosterone) levels in the blood were measured by ELISA kits.

Results

Antalarmin alleviated LPS-induced depression-like behaviour in male mice. Furthermore, antalarmin significantly inhibited changes in CRHR1, nectin3 and calbindin levels in the hippocampus and reduced the increase in CORT levels in LPS-treated mice.

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