ArticleAnnals of translational medicine2020
Effect of combined chronic predictable and unpredictable stress on depression-like symptoms in mice.
Article in Annals of translational medicine, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 68 citations in OpenAlex.
- Relationship Between Depression and Epigallocatechin Gallate from the Perspective of Gut Microbiota: A Systematic Review.Nutrients · 2025Pooled it
- Acute Hypoxic Exposure May Contribute to Depressive-Like Behaviors in Mice Through Disruption of Gut Microbiota Homeostasis.Alpha psychiatry · 2026Article
- Multisystem pathology in chronic variable stress: gut-liver-brain axis disruption and the therapeutic promise of magnesium-L-theanine.Therapeutic advances in endocrinology and metabolism · 2026Review
- Environmental enrichment attenuates chronic stress-induced disruptions in the gut microbiota, intestinal barrier, and brain.PloS one · 2026Article
- Puerarin's multidimensional antidepressant action: decoding the gut-liver-brain axis through gut microbiota, hepatic homeostasis, and neuroimmune regulation.Frontiers in neuroscience · 2026Article
- Antidepressant effect ofIBRO neuroscience reports · 2025Article
- Suramin protects against chronic stress-induced neurobehavioral deficits via cGAS-STING/NF-κB suppression.Scientific reports · 2025Article
- Sex differences in resilience at puberty depend upon divergent effects of a stress steroid at α4βδ GABABrain research · 2025Article
- Effect of Hesperidin on Chronic Unpredictable Mild Stress-Related Depression in Rats through Gut-Brain Axis Pathway.Chinese journal of integrative medicine · 2025Article
- Comparative analysis of two immunosuppression protocols for vulvovaginal candidiasis induction in Wistar rats.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2025Article
- A Study of Sex Differences in the Biological Pathways of Stress Regulation in Mice.CNS neuroscience & therapeutics · 2025Article
- The Role of the Neural Exposome as a Novel Strategy to Identify and Mitigate Health Inequities in Alzheimer's Disease and Related Dementias.Molecular neurobiology · 2025Review
- The effects of a semen cuscutae flavonoids-based antidepressant treatment on microbiome and metabolome in mice.Frontiers in microbiology · 2025Article
- Article
- A study on the differences in the gut microbiota and metabolism between male and female mice in different stress periods.Experimental biology and medicine (Maywood, N.J.) · 2025Article
- Identification and Validation of Antidepressant Small Molecules Using Bioinformatics and Mouse Depression Models.Drug design, development and therapy · 2025Article
- Article
- (-)-Syringaresinol Exerts an Antidepressant-like Activity in Mice by Noncompetitive Inhibition of the Serotonin Transporter.Pharmaceuticals (Basel, Switzerland) · 2024Article
- An Analysis of the Intestinal Microbiome Combined with Metabolomics to Explore the Mechanism of How Jasmine Tea Improves Depression in CUMS-Treated Rats.Foods (Basel, Switzerland) · 2024Article
- Antidepressant Effect of Enzymatic Porcine Placenta Hydrolysate in Repeated Immobilization Stress-Induced Ovariectomized Female Mice.Current issues in molecular biology · 2024Article
Corrections and comments
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Authors and funding
9 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundMental stress mainly induces depression, and predictable stress, as well as a constant bombardment of chronic unpredictable micro-stressors, always coexist in daily life. However, the combined effect of predictable and unpredictable stress on depression is still not fully understood.
methodsThe chronic restraint stress (CRS) is to restrain the mice for 6 h per day for 3 weeks, and the chronic unpredictable mild stress (CUMS) is to stimulate the mice with 7 different stressors for 3 weeks. We evaluated the combined effect of CRS and CUMS on depression-like symptoms using behavioral tests and investigated the action mechanism through analysis of neurotransmitters, brain-derived factors, inflammatory factors, antioxidants, and intestinal microorganisms.
resultsOur data suggested the combined stress of CRS and CUMS caused significant weight loss, food intake reduction, depression-like behaviors-including anhedonia, learned helplessness, and reduction in spontaneous activity-and even atrophy and severe structural damage to the hippocampus in mice. Our pathogenesis study showed that combined stress-induced the reduction of glucocorticoid receptor (GR) levels, loss of oligodendrocytes (NG2 and Olig2 cells), and inhibition of neuron proliferation in the CA1, CA3, and DG regions of the hippocampus, decreased the contents of monoamine neurotransmitters (5-HT and NE) and BDNF in the cerebral cortex, caused hyperactivity of the HPA system, led to immune dysfunction, aggravated oxidative stress, and weakened the capacity of antioxidants in mice. Compared with single stress, combined stress gave rise to a more significant diversity change of the gut microbiota.
conclusionsCombined stress caused significant depression-like behaviors, atrophy, and severe structural damage to the hippocampus in mice via monoamine neurotransmitter, BDNF, HPA axis, neurogenesis, and neurodegenerative, immune, oxidative stress and gut-brain axis action pathways.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.