ReviewFrontiers in neuroscience2014
Toll-like receptor 4: innate immune regulator of neuroimmune and neuroendocrine interactions in stress and major depressive disorder.
Review in Frontiers in neuroscience, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 69 papers, 2 of them syntheses 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
69 citing papers in PubMed, 2 syntheses or guidelines pooled it, 116 citations in OpenAlex.
- Unveiling the relationship of the comorbidity between depression and type 2 diabetes mellitus: a macro analysis and micro interpretation.Frontiers in medicine · 2026Pooled it
- Maternal acute and chronic inflammation in pregnancy is associated with common neurodevelopmental disorders: a systematic review.Translational psychiatry · 2021Pooled it
- Toll like receptor 4 (TLR4) in neuroinflammation: From acute hemorrhagic stroke to chronic neurodegeneration.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Associations of probiotics, prebiotics, synbiotics, and yogurt supplements with oxidative balance scores and all-cause and cardiovascular mortalities in neuropsychiatric disorders.American heart journal plus : cardiology research and practice · 2026Article
- The effects of alpha-pinene on anxiety behaviours and TLR4/MYD88/NF-kB pathway in the hippocampus in the reserpine-induced anxiety model in rats.Acta neuropsychiatrica · 2026Article
- Peripheral blood transcriptomic biomarkers for predicting antidepressant response in major depressive disorder.BMC psychiatry · 2026Article
- TLR4 mediates post-traumatic depression via kynurenine pathway activation in a murine traumatic brain injury model.Frontiers in pharmacology · 2026Article
- Article
- Psychosocial stress and cardiovascular disease.American journal of preventive cardiology · 2025Review
- Assessment of Protein Complex Predictions in CASP16: Are we making progress?bioRxiv : the preprint server for biology · 2025Article
- Down-regulation of HSPA9 reduces tyrosine hydroxylase-positive neurons in mouse substantia nigra and induces Parkinson's disease-like motor impairments.Animal cells and systems · 2025Article
- Dysregulation of the microbiota-gut-brain axis induced by chronic pancreatitis mediates anxiety- and depression-like behaviors in mice.Frontiers in immunology · 2025Article
- Associations of inflammation related prenatal adversities with neurodevelopment of offspring in one year: a longitudinal prospective birth cohort study.BMC pregnancy and childbirth · 2024Article
- Stress and cardiovascular disease: an update.Nature reviews. Cardiology · 2024Review
- The Role of Psychosocial Stress on Cardiovascular Disease in Women: JACC State-of-the-Art Review.Journal of the American College of Cardiology · 2024Review
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Neurosteroids and their potential as a safer class of general anesthetics.Journal of anesthesia · 2024Review
- The role of the Toll like receptor 4 signaling in sex-specific persistency of depression-like behavior in response to chronic stress.Brain, behavior, and immunity · 2024Article
- Novel neurosteroid therapeutics for post-partum depression: perspectives on clinical trials, program development, active research, and future directions.Neuropsychopharmacology : official publication of the American College of Neuropsychopharmacology · 2024Review
- Neurosteroid influence on affective tone.Neuroscience and biobehavioral reviews · 2023Review
9 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
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Major depressive disorder (MDD) poses one of the highest disease burdens worldwide. Yet, current treatments targeting serotonergic and noradrenaline reuptake systems are insufficient to provide long-term relief from depressive symptoms in most patients, indicating the need for new treatment targets. Having the ability to influence behavior similar to depressive symptoms, as well as communicate with neuronal and neuroendocrine systems, the innate immune system is a strong candidate for MDD treatments. Given the complex nature of immune signaling, the main question becomes: What is the role of the innate immune system in MDD? The current review presents evidence that toll-like receptor 4 (TLR4), via driving both peripheral and central immune responses, can interact with serotonergic neurotransmission and cause neuroendocrine disturbances, thus integrating with widely observed hallmarks of MDD. Additionally, through describing the multi-directional communication between immune, neural and endocrine systems in stress, TLR4-related mechanisms can mediate stress-induced adaptations, which are necessary for the development of MDD. Therefore, apart from exogenous pathogenic mechanisms, TLR4 is involved in immune changes as a result of endogenous stress signals, playing an integral part in the pathophysiology, and could be a potential target for pharmacological treatments to improve current interventions for MDD.
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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.