ArticleJournal of neurochemistry2013
IL-1β and TNF-α induce neurotoxicity through glutamate production: a potential role for neuronal glutaminase.
Article in Journal of neurochemistry, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 195 papers, 3 of them syntheses that pooled it.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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
195 citing papers in PubMed, 3 syntheses or guidelines pooled it, 363 citations in OpenAlex.
- Risk of dementia or Parkinson's disease in the presence of Sjögren's syndrome: A systematic review and meta-analysis.Frontiers in integrative neuroscience · 2022Pooled it
- Mitochondrial dysfunction, oxidative stress, neuroinflammation, and metabolic alterations in the progression of Alzheimer's disease: A meta-analysis of in vivo magnetic resonance spectroscopy studies.Ageing research reviews · 2021Pooled it
- Cytokines in cerebrospinal fluid of patients with schizophrenia spectrum disorders: New data and an updated meta-analysis.Schizophrenia research · 2018Pooled it
- Impact of Cannabidiol and Its Synthetic Derivative on Fentanyl Consumption and Fentanyl-Induced Neurometabolic Alterations in Mice.Molecules (Basel, Switzerland) · 2026Article
- Review
- Effect of Diabetic Neuropathy on Reparative Ability and Immune Response System.Molecular biotechnology · 2026Article
- Review
- The effect of gentiopicroside on brain tissue repair in mice during the acute phase of middle cerebral artery occlusion.Molecular biology reports · 2026Article
- A Developmental Taxonomy of Autism and the Precision Timing of the Cheung Glutamatergic Regimen.Cureus · 2026Review
- Pathological Roles of Astrocytes in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2026Review
- The lung-brain axis: elucidating the mechanisms of pulmonary-driven neurological disorders.Journal of neuroinflammation · 2026Review
- Modulation of Glutamate Release by Dexmedetomidine Preserves Dendritic Spines and Alleviates Cognitive Impairment in a Murine Model of Perioperative Neurocognitive Disorder.Neuroscience bulletin · 2026Article
- Neuro-Immune Crosstalk: Molecular Mechanisms, Biological Functions, Diseases, and Therapeutic Targets.MedComm · 2026Review
- Downregulation of the deubiquitinating enzyme USP10 correlates with neuronal apoptosis in HTLV-1-associated myelopathy.Scientific reports · 2026Article
- Acupuncture Activates PI3K/Akt Pathway to Promote Spinal Microglial M2 Polarization and Alleviate Spastic Hemiplegia Following Ischemic Stroke.Journal of inflammation research · 2026Article
- DXM, CYP2D6-inhibiting antidepressants, piracetam, and glutamine: proposing a ketamine-class antidepressant regimen with existing drugs.Frontiers in psychiatry · 2026Article
- Multi-omic spatially resolved analysis of the neuroinflammatory response to intracortical microelectrode arrays.Biomaterials · 2026Article
- Association between inflammatory markers and Parkinson's disease risk: a cross-sectional, propensity score-matched analysis of NHANES data.BMC neurology · 2025Article
- Evaluation of reserpine-induced fibromyalgia in mice: A comparative behavioral, neurochemical, and histological assessment of two doses.IBRO neuroscience reports · 2025Article
- State of the art: glioma-associated epilepsy-bridging tumor biology and epileptogenesis.Neurological research and practice · 2025Review
135 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
8 authors at 4 institutions in 2 countries.
Funding
Abstract
Glutaminase 1 is the main enzyme responsible for glutamate production in mammalian cells. The roles of macrophage and microglia glutaminases in brain injury, infection, and inflammation are well documented. However, little is known about the regulation of neuronal glutaminase, despite neurons being a predominant cell type of glutaminase expression. Using primary rat and human neuronal cultures, we confirmed that interleukin-1β (IL-1β) and tumor necrosis factor-α (TNF-α), two pro-inflammatory cytokines that are typically elevated in neurodegenerative disease states, induced neuronal death and apoptosis in vitro. Furthermore, both intracellular and extracellular glutamate levels were significantly elevated following IL-1β and/or TNF-α treatment. Pre-treatment with N-Methyl-D-aspartate (NMDA) receptor antagonist MK-801 blocked cytokine-induced glutamate production and alleviated the neurotoxicity, indicating that IL-1β and/or TNF-α induce neurotoxicity through glutamate. To determine the potential source of excess glutamate production in the culture during inflammation, we investigated the neuronal glutaminase and found that treatment with IL-1β or TNF-α significantly upregulated the kidney-type glutaminase (KGA), a glutaminase 1 isoform, in primary human neurons. The up-regulation of neuronal glutaminase was also demonstrated in situ in a murine model of HIV-1 encephalitis. In addition, IL-1β or TNF-α treatment increased the levels of KGA in cytosol and TNF-α specifically increased KGA levels in the extracellular fluid, away from its main residence in mitochondria. Together, these findings support neuronal glutaminase as a potential component of neurotoxicity during inflammation and that modulation of glutaminase may provide therapeutic avenues for neurodegenerative diseases.
Indexed as
Identifiers
What OpenQuestion holds
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.