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

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...

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Published in:BMC psychiatry 2023-01, Vol.23 (1), p.17-17, Article 17
Main Authors: Sun, Jie, Qiu, Lili, Zhang, Hui, Zhou, Zhiqiang, Ju, Lingsha, Yang, Jiaojiao
Format: Article
Language:English
Subjects:
Animals
Antidepressive Agents - pharmacology
Antidepressive Agents - therapeutic use
Care and treatment
Corticotropin releasing hormone
CRHR1
Depression - chemically induced
Depression - drug therapy
Depression, Mental
Depression-like behaviour
Disease Models, Animal
Health aspects
Hippocampus
HPA
Hypothalamo-Hypophyseal System - metabolism
Lipopolysaccharides
Male
Mice
Mice, Inbred C57BL
nectin3
Pituitary-Adrenal System - metabolism
Receptors, Corticotropin-Releasing Hormone - antagonists & inhibitors
Risk factors
Stress
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Summary: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. 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. 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. CRHR1antagonist showed antidepressant effects in LPS-induced depressive mice, and CRHR1/nectin3 signalling may play a crucial role in this process.
ISSN:1471-244X
1471-244X
DOI:10.1186/s12888-023-04519-z