How different lengths of long-term stress affect anxiety, depression, and brain-gut tryptophan metabolism in mice

One-week chronic restraint stress (CRS) resulted in decreased levels of neurotoxic metabolites and induced anxiety-like behaviors with neuroprotection in C57BL/6N mice.

• One-week CRS decreased open arm entries in the elevated plus maze and delayed feeding latency in the novelty suppressed feeding test.
• Four-week CRS reduced sucrose preference and increased immobility time in forced swimming tests, indicating heightened anxiety- and depression-like behaviors.
• One-week CRS showed decreased levels of neurotoxic 3-hydroxykynurenine and quinolinic acid, alongside increased kynurenic acid in the hippocampus.
• In contrast, four-week CRS resulted in reduced kynurenic acid and increased levels of neurotoxic metabolites in the hippocampus.
• Both one-week and four-week CRS led to significant reductions in neurotoxic metabolites in the colon, with a notable increase in kynurenic acid observed only in four-week CRS mice.
• Four-week CRS is associated with increased risk of intestinal inflammation, while short-term stress may have protective effects.

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