Effects of different chronic restraint stress periods on anxiety- and depression-like behaviors and tryptophan-kynurenine metabolism along the brain-gut axis in C57BL/6N mice

• Published in: European journal of pharmacology Vol. 965; p. 176301
• Main Authors: Ye, Fan, Dong, Meng-Chen, Xu, Chen-Xi, Jiang, Ning, Chang, Qi, Liu, Xin-Min, Pan, Rui-Le
• Format: Journal Article
• Language: English
• Published: Netherlands 15.02.2024
• Subjects: Tryptophan-kynurenine metabolism; Anxiety-like behavior; Depression-like behavior; Chronic restraint stress; Brain-gut axis
• ISSN: 0014-2999; 1879-0712
• DOI: 10.1016/j.ejphar.2023.176301

Chronic restraint stress (CRS) is a widely used stimulus to induce anxiety- and depression-like behaviors, linked to alterations in tryptophan-kynurenine (TRP-KYN) metabolism in animals. This study assessed the effects of different CRS periods on anxiety- or depression-like behaviors and TRP-KYN metabolism along brain-gut axis in C57BL/6N mice. Results showed that one-week CRS decreased the open arm entries of mice in elevated plus maze and delayed latency of feeding in novelty suppressed feeding test. Four-week CRS reduced sucrose preference, increases forced swimming immobility time, and also induced anxiety-like behaviors of mice. UPLC-MS/MS analysis revealed decreased levels of the neurotoxic 3-hydroxykynurenine (3-HK) and quinolinic acid (QA), and an increase in the neuroprotective kynurenic acid (KA) in the hippocampus of one-week CRS mice; meanwhile, four-week CRS mice displayed a reduction in KA and increases in 3-HK and QA. In the colon, both one-week and four-week CRS mice exhibited significant reductions in 3-HK and QA, with a marked increase of KA exclusively in four-week CRS mice. Briefly, one-week CRS only induced anxiety-like behaviors with hippocampal neuroprotection in TRP-KYN metabolism, whereas four-week CRS caused anxiety- and depression-like behaviors with neurotoxicity. In the colon, during both CRS periods, KYN was metabolized in the direction of NAD production. However, four-week CRS triggered intestinal inflammation risk with increased KA. Summarily, slightly short-term stress has beneficial effects on mice, while prolonged chronic stress can lead to pathological changes. This study offers valuable insights into stress-induced emotional disturbances.