ArticleFrontiers in neuroscience2025
Chronic unpredictable mild stress induces anxiety-like behavior in female C57BL/6N mice, accompanied by alterations in inflammation and the kynurenine pathway of tryptophan metabolism.
Article in Frontiers in neuroscience, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- Chronic unpredictable mild Stress- induced neurobehavioral and metabolic alteration: insights into molecular mechanisms and emerging therapeutic Strategies".Psychopharmacology · 2026Review
- Protective Effects ofPharmaceuticals (Basel, Switzerland) · 2026Article
- Analysis of gut microbiota and intestinal mucosal neurotransmitter changes and their correlation in adolescent depression mice.Annals of general psychiatry · 2026Article
- Metabolic Reprogramming of Microglia in Neuroinflammation and Depression.International journal of molecular sciences · 2026Review
- Interplay of Vitamin D3, Wnt/β-Catenin Pathway, and Oxidative DNA Injury in CMS-Induced Depression Model.Biomedicines · 2026Article
- Modulation of the Kynurenine Pathway: A New Approach for Treating Neurodegeneration.Life (Basel, Switzerland) · 2026Review
- The kynurenine pathway in depression and schizophrenia: convergent signals, divergent states, and clinical signatures.EXCLI journal · 2026Review
- Environmental enrichment attenuates chronic stress-induced disruptions in the gut microbiota, intestinal barrier, and brain.PloS one · 2026Article
- Neuromodulatory Effects of Arecoline on Anxiety-like Behavior in Mice Exposed to Chronic Unpredictable Mild Stress.International journal of molecular sciences · 2025Article
- Electroacupuncture attenuates anxiety caused by chronic mild stress through inhibiting NOX2-derived oxidative stress in ventral hippocampus.Neurobiology of stress · 2025Article
- Molecular Crosstalk of Vitamin D3 with cGAS-STING and BDNF Pathways in a Rat Model of Chronic Stress.International journal of molecular sciences · 2025Article
- Neurobiological Correlates of Coping Strategies in PTSD: The Role of IGF-1, CASP-9, nNOS, and IL-10 Based on Brief-COPE Assessment.Current issues in molecular biology · 2025Article
- The therapeutic effects ofGut microbiome (Cambridge, England) · 2025Review
- The central role of microglia in major depressive disorder and its potential as a therapeutic target.Frontiers in behavioral neuroscience · 2025Review
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Authors and funding
11 authors.
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Abstract
Chronic stress can impact brain function through various mechanisms, contributing to the development of anxiety disorders. Chronic unpredictable mild stress (CUMS) is a well-established model for studying the effects of chronic stress. This study assessed the impacts of different durations of CUMS on anxiety-like behavior, inflammation, and tryptophan metabolism in female C57BL/6N mice. The results revealed significant behavioral changes after 2-4 weeks of CUMS. Specifically, the open arms ratio and open arms time ratio in the elevated plus maze (EPM) decreased, the latency to feed in the novelty-suppressed feeding test (NSFT) was prolonged, and the number of transitions in the light/dark box (LDB) was decreased. After 1 week of CUMS, the levels of some pro-inflammatory cytokines (such as IL-1β and iNOS) and anti-inflammatory cytokines (including IL-10) began to rise. After 2 weeks of CUMS, most pro-inflammatory cytokines (IL-1β, IL-6, CD86, iNOS) and the anti-inflammatory cytokines TGF-β and CD11b showed an increase, while some anti-inflammatory cytokines (Arg-1, IL-10) began to decrease. After 3 weeks of stress, the pro-inflammatory cytokine TNF-α also significantly increased, while the anti-inflammatory cytokine TGF-β began to decline. By 4 weeks of CUMS, the anti-inflammatory cytokine CD11b also started to decrease. Regarding tryptophan metabolism, after 3-4 weeks of CUMS, serotonin (5-HT) levels in the hippocampus of the mice began to decrease. Additionally, the kynurenine pathway in tryptophan metabolism shifted more towards the KYN-QA branch, resulting in the reduction in the neuroprotective substance kynurenic acid (KYNA), while neurotoxic substances such as 3-hydroxykynurenine (3-HK) and quinolinic acid (QA) accumulated. In summary, female C57BL/6N mice exhibit anxiety-like behavior after 2 weeks of CUMS, accompanied by inflammatory responses. After 3-4 weeks of CUMS, anxiety-like behavior persists, with exacerbated inflammatory responses and disturbances in tryptophan metabolism.
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