ArticleCell death & disease2021
Neuroinflammation induces synaptic scaling through IL-1β-mediated activation of the transcriptional repressor REST/NRSF.
Article in Cell death & disease, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. An erratum has been issued. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 52 citations in OpenAlex.
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- Molecular Mechanisms of Hippocampal Synaptic Plasticity Disruption Induced by Chronic Methamphetamine Exposure: A Narrative Review.Cellular and molecular neurobiology · 2026Review
- Inflammatory stimulus enhances synaptic material uptake by adult APP microglia in a microfluidic neuron-microglia co-culture model.Journal of neuroinflammation · 2026Article
- KCC2 Dysfunction Mediated by Microglial BDNF/TrkB Signaling Exacerbates Early Post-Stroke Seizure Susceptibility.CNS neuroscience & therapeutics · 2026Article
- Effect of inspired oxygen fraction during anesthesia on inflammation and antioxidant enzyme activity in the mouse cortex and hippocampus.Frontiers in aging neuroscience · 2026Article
- The Dynamic Roles of Repressor Element 1-Silencing Transcription Factor (REST): A Double-Edged Sword in Neural Health and Disease.Molecular neurobiology · 2025Review
- The interplay between metabolism and neuroinflammation in epilepsy: mechanisms and therapeutic perspectives.Journal of neuroinflammation · 2025Review
- Harnessing metabolic control for synaptic stability: REST/NRSF links glycolytic inhibition to excitatory neurotransmission.The Journal of physiology · 2025Article
- Effects ofJournal of microbiology and biotechnology · 2025Article
- Understanding monocyte-driven neuroinflammation in Alzheimer's disease using human cortical organoid microphysiological systems.Science advances · 2025Article
- Pinealectomy-Induced Neuroinflammation Varies with Age in Rats.International journal of molecular sciences · 2025Article
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- The restoration of REST inhibits reactivity of Down syndrome iPSC-derived astrocytes.Frontiers in molecular neuroscience · 2025Article
- The Potential Protective Effects of EGCG Against Epilepsy-Induced Damage in Rats by Mitigating Oxidative Stress, Inflammation, and Apoptosis.Scientifica · 2025Article
- Microglia-orchestrated neuroinflammation and synaptic remodeling: roles of pro-inflammatory cytokines and receptors in neurodegeneration.Frontiers in cellular neuroscience · 2025Review
- Promotive effect of skin precursor-derived Schwann cells on brachial plexus neurotomy and motor neuron damage repair through milieu-regulating secretome.Regenerative therapy · 2024Article
- Enduring memory consequences of early-life stress / adversity: Structural, synaptic, molecular and epigenetic mechanisms.Neurobiology of stress · 2024Review
Corrections and comments
- Erratum issued
Authors and funding
11 authors at 5 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Neuroinflammation is associated with synapse dysfunction and cognitive decline in patients and animal models. One candidate for translating the inflammatory stress into structural and functional changes in neural networks is the transcriptional repressor RE1-silencing transcription factor (REST) that regulates the expression of a wide cluster of neuron-specific genes during neurogenesis and in mature neurons. To study the cellular and molecular pathways activated under inflammatory conditions mimicking the experimental autoimmune encephalomyelitis (EAE) environment, we analyzed REST activity in neuroblastoma cells and mouse cortical neurons treated with activated T cell or microglia supernatant and distinct pro-inflammatory cytokines. We found that REST is activated by a variety of neuroinflammatory stimuli in both neuroblastoma cells and primary neurons, indicating that a vast transcriptional change is triggered during neuroinflammation. While a dual activation of REST and its dominant-negative splicing isoform REST4 was observed in N2a neuroblastoma cells, primary neurons responded with a pure full-length REST upregulation in the absence of changes in REST4 expression. In both cases, REST upregulation was associated with activation of Wnt signaling and increased nuclear translocation of β-catenin, a well-known intracellular transduction pathway in neuroinflammation. Among single cytokines, IL-1β caused a potent and prompt increase in REST transcription and translation in neurons, which promoted a delayed and strong synaptic downscaling specific for excitatory synapses, with decreased frequency and amplitude of spontaneous synaptic currents, decreased density of excitatory synaptic connections, and decreased frequency of action potential-evoked Ca
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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 Socratic graph.