ArticleBrain, behavior, and immunity2018
Complement component 3a receptor deficiency attenuates chronic stress-induced monocyte infiltration and depressive-like behavior.
Article in Brain, behavior, and immunity, 2018. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 64 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
64 citing papers in PubMed, 1 synthesis or guideline pooled it, 116 citations in OpenAlex.
- Association of Kawasaki disease with intellectual disability, attention deficit hyperactivity disorder, and autism spectrum disorder: a systematic review and meta-analysis.Italian journal of pediatrics · 2025Pooled it
- Liver-derived complement component 3 promotes the susceptibility to stress-induced depression by impairing blood-brain barrier integrity.Molecular psychiatry · 2026Article
- A Synergistic Hydrogel-Microalgae Platform for Dual-Targeting of Intestinal and Neuroimmune Dysfunction in Inflammatory Bowel Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2026Article
- Panacis Quinquefolii Radix Polysaccharides Alleviate Depressive-Like Behaviors in Chronic Unpredictable Mild Stress-Induced Mice by Suppressing Complement C1Q/C3-Mediated Microglial Synaptic Pruning and Modulating Gut Microbiota.CNS neuroscience & therapeutics · 2026Article
- Ozone-induced cognitive deficits are mediated by the liver-brain axis: peripheral complement C3 triggers microglial synaptic phagocytosis.Journal of neuroinflammation · 2026Article
- Clinical Factors and Serum Biomarkers Associated With Major Depressive Disorder in Adolescents With and Without Nonsuicidal Self-Injury: A Comparative Cross-Sectional Study.Alpha psychiatry · 2026Article
- Opposing roles of microglial and macrophagic C3ar1 signaling in stress-induced synaptic and behavioral changes.Molecular psychiatry · 2025Article
- Review
- Targeting the complement-mTOR-autophagy axis: the role of apolipoprotein E in depression.BMC biology · 2025Article
- Chronic stress induces depression-like behaviors and Parkinsonism via upregulating α-synuclein.NPJ Parkinson's disease · 2025Article
- Linking Kawasaki Disease to Mental Health: A Nationwide Study on Long-Term Neurological Risks.Medicina (Kaunas, Lithuania) · 2025Article
- Microglial type I interferon signaling mediates chronic stress-induced synapse loss and social behavior deficits.Molecular psychiatry · 2025Article
- Complement receptorBrain communications · 2025Article
- From trauma to depression: structural, synaptic, epigenetic, and molecular pathways linking early stress to lifelong vulnerability.Frontiers in psychiatry · 2025Review
- Targeting complement C3 with Tanshinone I decreases microglia-mediated synaptic engulfment to exert antidepressant effects.Theranostics · 2025Article
- (Re)building the nervous system: A review of neuron-glia interactions from development to disease.Journal of neurochemistry · 2025Review
- Article
- Complement and microglia activation mediate stress-induced synapse loss in layer 2/3 of the medial prefrontal cortex in male mice.Nature communications · 2024Article
- Overexpression of the schizophrenia risk gene C4 in PV cells drives sex-dependent behavioral deficits and circuit dysfunction.iScience · 2024Article
- Ketamine's mechanism of action with an emphasis on neuroimmune regulation: can the complement system complement ketamine's antidepressant effects?Molecular psychiatry · 2024Review
4 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
Abstract
Major depressive disorder (MDD) is one of the most common and debilitating neuropsychiatric illnesses. Accumulating evidence suggests a potential role of the immune system in the pathophysiology of MDD. The complement system represents one of the major effector mechanisms of the innate immune system, and plays a critical role in inflammation. However, the role of complement components in MDD is not well understood. Here, we found significant increase in component 3 (C3) expression in the prefrontal cortex (PFC) of depressed suicide subjects. We tested the role of altered C3 expression in mouse model of depression and found that increased C3 expression in PFC as a result of chronic stress causes depressive-like behavior. Conversely, mice lacking C3 were resilient to stress-induced depressive-like behavior. Moreover, selective overexpression of C3 in PFC was sufficient to cause depressive-like behavior in mice. We found that C3a (activated product of C3) receptor, C3aR+ monocytes were infiltrated into PFC following chronic stress. However, C3aR knockout mice displayed significantly reduced monocyte recruitment into PFC and reduced levels of the proinflammatory cytokine IL-1β in PFC after chronic stress. In addition, C3aR knockout mice did not exhibit chronic stress-induced behavior despair. Similarly, chronic stress-induced increases in C3aR+ monocytes and IL-1β in PFC, and depressive-like behavior were attenuated by myeloid cell depletion. These postmortem and preclinical studies identify C3aR signaling as a key factor in MDD pathophysiology.
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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.