ArticlePloS one2012
Glia-pinealocyte network: the paracrine modulation of melatonin synthesis by tumor necrosis factor (TNF).
Article in PloS one, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 33 papers.
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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.
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Who cites it
33 citing papers in PubMed, 113 citations in OpenAlex.
- Rhythmic patterns in microglial cells within the circadian pineal gland from male rats.Anatomical record (Hoboken, N.J. : 2007) · 2026Article
- Circadian Rhythms in Acute Respiratory Distress Syndrome: Molecular Mechanisms and Therapeutic Implications.International journal of molecular sciences · 2026Review
- Age-Related Changes as the Primary Driver of Pineal Gland Involution-A Morphological Study in Health and Disease.International journal of molecular sciences · 2026Article
- Peripheral metabolic-redox signaling as a core mechanism of major depressive disorder: evidence from deep metabolomic phenotyping.Acta neuropsychiatrica · 2026Article
- Functional shotgun metagenomic insights into gut microbial pathway and enzyme disruptions linking metabolism, affect, cognition, and suicidal ideation in major depressive disorder.Acta neuropsychiatrica · 2026Article
- Association between body roundness index and sleep disorder: the mediating role of depression.BMC psychiatry · 2025Article
- Effect of season on histoarchitecture of pineal gland in buffalo (Iranian journal of veterinary research · 2024Article
- Melatonin, BAG-1 and cortisol circadian interactions in tumor pathogenesis and patterned immune responses.Exploration of targeted anti-tumor therapy · 2023Review
- Possible Role of Pineal and Extra-Pineal Melatonin in Surveillance, Immunity, and First-Line Defense.International journal of molecular sciences · 2021Review
- Melatonin and Microglia.International journal of molecular sciences · 2021Review
- Molecular links between endocrine, nervous and immune system during chronic stress.Brain and behavior · 2021Review
- Lipopolysaccharide Regulates Pro- and Anti-Inflammatory Cytokines, Corticosterone, and Melatonin in Toads.Integrative organismal biology (Oxford, England) · 2021Article
- Melatonin and Depression: A Translational Perspective From Animal Models to Clinical Studies.Frontiers in psychiatry · 2021Review
- Sleep deprivation aggravated lipopolysaccharide/D-galactosamine-induced acute liver injury by suppressing melatonin production.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2020Article
- Melatonin and cortisol exhibit different circadian rhythm profiles during septic shock depending on timing of onset: a prospective observational study.Annals of intensive care · 2018Article
- Differential response of pineal microglia to surgical versus pharmacological stimuli.The Journal of comparative neurology · 2018Article
- Immune-pineal axis - acute inflammatory responses coordinate melatonin synthesis by pinealocytes and phagocytes.British journal of pharmacology · 2018Review
- β-Adrenoceptors Trigger Melatonin Synthesis in Phagocytes.International journal of molecular sciences · 2018Article
- Pineal Calcification, Melatonin Production, Aging, Associated Health Consequences and Rejuvenation of the Pineal Gland.Molecules (Basel, Switzerland) · 2018Review
- Article
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The pineal gland, a circumventricular organ, plays an integrative role in defense responses. The injury-induced suppression of the pineal gland hormone, melatonin, which is triggered by darkness, allows the mounting of innate immune responses. We have previously shown that cultured pineal glands, which express toll-like receptor 4 (TLR4) and tumor necrosis factor receptor 1 (TNFR1), produce TNF when challenged with lipopolysaccharide (LPS). Here our aim was to evaluate which cells present in the pineal gland, astrocytes, microglia or pinealocytes produced TNF, in order to understand the interaction between pineal activity, melatonin production and immune function. Cultured pineal glands or pinealocytes were stimulated with LPS. TNF content was measured using an enzyme-linked immunosorbent assay. TLR4 and TNFR1 expression were analyzed by confocal microscopy. Microglial morphology was analyzed by immunohistochemistry. In the present study, we show that although the main cell types of the pineal gland (pinealocytes, astrocytes and microglia) express TLR4, the production of TNF induced by LPS is mediated by microglia. This effect is due to activation of the nuclear factor kappa B (NF-kB) pathway. In addition, we observed that LPS activates microglia and modulates the expression of TNFR1 in pinealocytes. As TNF has been shown to amplify and prolong inflammatory responses, its production by pineal microglia suggests a glia-pinealocyte network that regulates melatonin output. The current study demonstrates the molecular and cellular basis for understanding how melatonin synthesis is regulated during an innate immune response, thus our results reinforce the role of the pineal gland as sensor of immune status.
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Registered trials
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