ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2013
TNF-α downregulates inhibitory neurotransmission through protein phosphatase 1-dependent trafficking of GABA(A) receptors.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 147 papers.
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
147 citing papers in PubMed, 231 citations in OpenAlex.
- Antiepileptic and antiepileptogenic effects ofIBRO neuroscience reports · 2026Article
- Motor cortex pain compensation is modifiable: allostatic load degrades its analgesic efficiency and rehabilitation restores it.medRxiv : the preprint server for health sciences · 2026Article
- TNF-dependent regulation of synaptic plasticity and neuronal activity: implications for psychiatric disorders.Molecular psychiatry · 2026Review
- The Molecular Machinery of Synaptic Plasticity and Its Potential Role in the Aetiology of Schizophrenia.Molecular neurobiology · 2026Review
- Lymphocyte subpopulations and EEG asymmetry.Journal of neural transmission (Vienna, Austria : 1996) · 2026Article
- Impact of Sema3A Interference on Cerebellum-Dependent Motor Associative Learning and Memory.International journal of molecular sciences · 2026Article
- Review
- TNF-α and IFN-γ impair neural oscillations and induce neurodegeneration by microglial nitric oxide, metabolic and oxidative stress.Journal of neuroinflammation · 2026Article
- Neurovascular and synaptic milieu of brain-resident cells in cognitive dysfunction of myalgic encephalomyelitis/chronic fatigue syndrome.Journal of translational medicine · 2026Review
- Sex differences in behaviors, neuronal activation, and gut-microbiota-metabolic axis in a repeated nitroglycerin-induced chronic migraine model.The journal of headache and pain · 2026Article
- Selective Inhibition of Tumor Necrosis Factor for Attenuating Alzheimer's Disease: Strategies Targeting Neuroinflammation.Inflammation · 2026Review
- Social exclusion in educational settings and the risk of alienation in adolescent development: a narrative review from a mind-body interaction perspective.Frontiers in psychology · 2026Review
- Short-term continuous light exposure induces hippocampal rhythmic and functional alterations: a multi-timepoint metabolomics study.Frontiers in molecular biosciences · 2026Article
- Neuroendocrine-immune perturbations in metabolic disease: pathophysiological mechanisms underlying cognitive impairment.Frontiers in human neuroscience · 2026Review
- Reframing brain aging: neuroinflammation as an interconnected network process.Frontiers in aging · 2026Review
- The missing link: TNF-α as a unifying mechanism in methamphetamine-induced neuronal dysfunction and blood-brain barrier compromise.Journal of neuroimmunology · 2025Review
- Methylprednisolone Restores Cognitive Impairment in mdx Mice by Inhibiting NF-κB/CCL5-mediated Neuroinflammation.Molecular neurobiology · 2025Article
- From Neurotransmission to Retinal Pathophysiology: Unraveling the Role of GABA Receptors in Retinal Disease Progression.Journal of neurochemistry · 2025Review
- Changes in Neuroimmunological Synapses During Cerebral Ischemia.Translational stroke research · 2025Review
- Potential roles for microglia in drug addiction: Adolescent neurodevelopment and beyond.Journal of neuroimmunology · 2025Review
87 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
2 authors at 1 institution in 1 country.
Funding
Abstract
Inflammation has been implicated in the progression of neurological disease, yet precisely how inflammation affects neuronal function remains unclear. Tumor necrosis factor-α (TNFα) is a proinflammatory cytokine that regulates synapse function by controlling neurotransmitter receptor trafficking and homeostatic synaptic plasticity. Here we characterize the mechanisms through which TNFα regulates inhibitory synapse function in mature rat and mouse hippocampal neurons. Acute application of TNFα induces a rapid and persistent decrease of inhibitory synaptic strength and downregulation of cell-surface levels of GABA(A)Rs containing α1, α2, β2/3, and γ2 subunits. We show that trafficking of GABA(A)Rs in response to TNFα is mediated by neuronally expressed TNF receptor 1 and requires activation of p38 MAPK, phosphatidylinositol 3-kinase, protein phosphatase 1 (PP1), and dynamin GTPase. Furthermore, TNFα enhances the association of PP1 with GABA(A)R β3 subunits and dephosphorylates a site on β3 known to regulate phospho-dependent interactions with the endocytic machinery. Conversely, we find that calcineurin and PP2A are not essential components of the signaling pathway and that clustering of the scaffolding protein gephyrin is only reduced after the initial receptor endocytosis. Together, these findings demonstrate a distinct mechanism of regulated GABA(A)R endocytosis that may contribute to the disruption of circuit homeostasis under neuroinflammatory conditions.
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.