ArticleJournal of neurochemistry2015
Rapid mitochondrial dysfunction mediates TNF-alpha-induced neurotoxicity.
Article in Journal of neurochemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 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.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 152 citations in OpenAlex.
- Effects of chemotherapy for acute lymphoblastic leukemia on cognitive function in animal models of contemporary protocols: A systematic literature review.Neuroscience and biobehavioral reviews · 2021Pooled it
- Anti-Inflammatory and Antioxidant Strategies in Epilepsy: From Molecular Mechanisms to Threshold Management.International journal of molecular sciences · 2026Review
- Cytokines at the Crossroads of Mitochondrial Dysfunction and Inflammation in Colorectal Cancer: Implications for Postoperative Complications.Molecular diagnosis & therapy · 2026Review
- Pathological Roles of Astrocytes in Traumatic Brain Injury.CNS neuroscience & therapeutics · 2026Review
- Hesperidin Attenuates H₂O₂-Induced Neurotoxicity via Modulation of Inflammatory Pathways and MMP Activity in Differentiated SH-SY5Y Cells: In Vitro and In Silico Models.Journal of biochemical and molecular toxicology · 2026Article
- The Role of TNF-α in Ischemic Stroke.International journal of molecular sciences · 2026Review
- Tumor necrosis factor alpha triggers mitochondrial dysfunction and ROS-driven cytokine amplification in bovine fibroblast-like synoviocytes.Frontiers in veterinary science · 2026Article
- Effects of Diet and Exercise on Mitochondrial Health in Metabolic Dysfunction-Associated Steatotic Liver Disease (MASLD): Role of Ceramides.Nutrients · 2025Review
- Mechanism of action behind the pain-relief effects of extracellular vesicles in microfragmented adipose tissue: an in vitro and in vivo study.Journal of translational medicine · 2025Article
- Article
- Comparative Effects of Tumor Necrosis Factor Alpha, Lipopolysaccharide, and Palmitate on Mitochondrial Dysfunction in Cultured 3T3-L1 Adipocytes.Cell biochemistry and biophysics · 2025Article
- Recent development of mitochondrial metabolism and dysfunction in osteoarthritis.Frontiers in pharmacology · 2025Review
- Impaired endothelial function contributes to cardiac dysfunction: role of mitochondrial dynamics.American journal of physiology. Heart and circulatory physiology · 2025Review
- Eye on the horizon: The metabolic landscape of the RPE in aging and disease.Progress in retinal and eye research · 2025Review
- Differentiation and regulation of CD4Cellular and molecular life sciences : CMLS · 2024Review
- A comprehensive review on the neuroprotective potential of resveratrol in ischemic stroke.Heliyon · 2024Review
- Review
- The neuroprotective effects of normobaric oxygen therapy after stroke.CNS neuroscience & therapeutics · 2024Review
- The Role of the Complement System in Synaptic Pruning after Stroke.Aging and disease · 2024Review
- Review
27 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Tumor necrosis factor alpha (TNF-α) is known to exacerbate ischemic brain injury; however, the mechanism is unknown. Previous studies have evaluated the effects of TNF-α on neurons with long exposures to high doses of TNF-α, which is not pathophysiologically relevant. We characterized the rapid effects of TNF-α on basal respiration, ATP production, and maximal respiration using pathophysiologically relevant, post-stroke concentrations of TNF-α. We observed a reduction in mitochondrial function as early as 1.5 h after exposure to low doses of TNF-α, followed by a decrease in cell viability in HT-22 cells and primary neurons. Subsequently, we used the HT-22 cell line to determine the mechanism by which TNF-α causes a rapid and profound reduction in mitochondrial function. Pre-treating with TNF-R1 antibody, but not TNF-R2 antibody, ameliorated the neurotoxic effects of TNF-α, indicating that TNF-α exerts its neurotoxic effects through TNF-R1. We observed an increase in caspase 8 activity and a decrease in mitochondrial membrane potential after exposure to TNF-α which resulted in a release of cytochrome c from the mitochondria into the cytosol. These novel findings indicate for the first time that an acute exposure to pathophysiologically relevant concentrations of TNF-α has neurotoxic effects mediated by a rapid impairment of mitochondrial function. This study focuses on the neurotoxic mechanism of a pro-inflammatory cytokine, tumor necrosis factor alpha (TNF-α). We demonstrate a prompt mitochondrial dysfunction followed by nerve cell loss after exposure to TNF-α. These studies may provide evidence that the immune system can rapidly and adversely affect brain function and that TNF-α signaling may be a target for neuroprotection.
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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.