ArticleTranslational psychiatry2024
Down-regulation of MKP-1 in hippocampus protects against stress-induced depression-like behaviors and neuroinflammation.
Article in Translational psychiatry, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 26 citations in OpenAlex.
- Neuroprotective and Antidepressant Effects ofExperimental neurobiology · 2026Article
- Neuroinflammation in Epilepsy: Biochemical and Molecular Mechanisms and Implications for Natural Product-Driven Drug Discovery.International journal of molecular sciences · 2026Review
- Cell-type and spatiotemporal transcriptional signatures of white matter morphometric similarity network alterations in major depressive disorder.Psychological medicine · 2026Article
- Molecular Mechanisms of Mangiferin on Neuroinflammation for Treating Major Depressive Disorder Based on Network Pharmacology and Bioinformatics Analysis.Journal of neuroimmune pharmacology : the official journal of the Society on NeuroImmune Pharmacology · 2026Article
- Behavioral, antioxidant, and kynurenine pathway modulation of a specific strain of Ligilactobacillus salivarius in a preclinical model of depression.European journal of nutrition · 2026Article
- Spatial multiomics dissects the SARS-CoV-2-induced disruption of cell adhesion and immune dynamics in the human hippocampus.Journal of neuroinflammation · 2026Article
- Identification and functional characterization of plasma exosomal miR-618 as a novel biomarker in recurrent depressive disorder.Frontiers in pharmacology · 2026Article
- Identification of AICD-associated transcriptomic markers in major depressive disorder.Frontiers in psychiatry · 2026Article
- Parallel Pathways, Divergent Outcomes: Adipose Tissue-Neural Crosstalk in Depression and Obesity.Journal of clinical medicine · 2025Review
- Standardized rice bran supplement ameliorates depressive behaviors via FKBP5 mediated glucocorticoid receptor signaling.NPJ science of food · 2025Article
- Identification of Key Ferroptosis-Related Genes as Potential Diagnostic Biomarkers for Ischemic Stroke: Evidences from Integrated Bioinformatics Analysis and Experiments.Cellular and molecular neurobiology · 2025Article
- Neurobiological subtypes of adolescent depression: a multimodal integration of morphometric similarity network and spatial transcriptomics.Molecular psychiatry · 2025Article
- Chronic Stress Modulates Microglial Activation Dynamics, Shaping Priming Responses to Subsequent Stress.Brain sciences · 2025Article
- Effects of Ninjin'yoeito and physical exercise on serum corticosterone and hippocampal BDNF/proBDNF and neuroinflammation in post-stroke depression in rats.BMC complementary medicine and therapies · 2025Article
- Article
- Role of sirtuin 1 in depression‑induced coronary heart disease: Molecular pathways and therapeutic potential (Review).Biomedical reports · 2025Review
- A Novel Mouse Model of Depression: Advantages in Immune Research and Clinical Translation.International journal of biological sciences · 2025Article
- Neuroinflammation and stress-induced pathophysiology in major depressive disorder: mechanisms and therapeutic implications.Frontiers in cellular neuroscience · 2025Review
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Authors and funding
15 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Chronic stress is the primary environmental risk factor for major depressive disorder (MDD), and there is compelling evidence that neuroinflammation is the major pathomechanism linking chronic stress to MDD. Mitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1) is a negative regulator of MAPK signaling pathways involved in cellular stress responses, survival, and neuroinflammation. We examined the possible contributions of MKP-1 to stress-induced MDD by comparing depression-like behaviors (anhedonia, motor retardation, behavioral despair), neuroinflammatory marker expression, and MAPK signaling pathways among rats exposed to chronic unpredictable mild stress (CUMS), overexpressing MKP-1 in the hippocampus, and CUMS-exposed rats underexpressing MKP-1 in the hippocampus. Rats exposed to CUMS exhibited MKP-1 overexpression, greater numbers of activated microglia, and enhanced expressions of neuroinflammatory markers (interleukin [IL]-6, [IL]-1β, tumor necrosis factor [TNF]-ɑ, and decreased phosphorylation levels of ERK and p38 in the hippocampus as well as anhedonia in the sucrose preference test, motor retardation in the open field, and greater immobility (despair) in the forced swimming tests. These signs of neuroinflammation and depression-like behaviors and phosphorylation levels of ERK and p38 were also observed in rats overexpressing MKP-1 without CUMS exposure, while CUMS-induced neuroinflammation, microglial activation, phosphorylation levels of ERK and p38, and depression-like behaviors were significantly reversed by MKP-1 knockdown. Moreover, MKP-1 knockdown promoted the activation of the MAPK isoform ERK, implying that the antidepressant-like effects of MKP-1 knockdown may be mediated by the ERK pathway disinhibition. These findings suggested that hippocampal MKP-1 is an essential regulator of stress-induced neuroinflammation and a promising target for antidepressant development.
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