ArticleJournal of neuroinflammation2015
Activation of toll like receptor 4 attenuates GABA synthesis and postsynaptic GABA receptor activities in the spinal dorsal horn via releasing interleukin-1 beta.
Article in Journal of neuroinflammation, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
What it found
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Who cites it
47 citing papers in PubMed, 73 citations in OpenAlex.
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- KRAS/ACTN4/p65-NR2A axis mediates glutamine-glutamate metabolic coupling between schwann cells and pancreatic cancer promoting perineural invasion.Journal of advanced research · 2026Article
- The association between medial prefrontal GABA concentration and memory performance is disrupted in human with a high body mass index.Brain imaging and behavior · 2026Article
- ADAM17 Supports Disinhibition of Pre-sympathetic Glutamatergic Neurons Through Microglial Chemotaxis.Neuroscience bulletin · 2026Article
- Nociplastic pain: the prominent role of non-neuronal cells in central and peripheral sensitization.Frontiers in immunology · 2026Review
- Neural Correlates of Burnout Syndrome Based on Electroencephalography (EEG)-A Mechanistic Review and Discussion of Burnout Syndrome Cognitive Bias Theory.Journal of clinical medicine · 2025Review
- Functional Foods Alleviate Behavioral Alterations and Improve GABAergic System Regulating TLR-4/NF-κB Axis in Valproic-Induced Autism.Brain and behavior · 2025Article
- Modulation of adult hippocampal neurogenesis by interleukin 1 signaling.Neurobiology of sleep and circadian rhythms · 2025Article
- Interleukin-1β depresses neuronal activity in the rat olfactory bulb even during odor stimulation.PloS one · 2025Article
- The role of the neuroinflammation and stressors in premenstrual syndrome/premenstrual dysphoric disorder: a review.Frontiers in endocrinology · 2025Review
- Microglia in neuroimmunopharmacology and drug addiction.Molecular psychiatry · 2024Review
- Emerging Molecular and Synaptic Targets for the Management of Chronic Pain Caused by Systemic Lupus Erythematosus.International journal of molecular sciences · 2024Review
- Disinhibition does not play a role in endomorphin-2-induced changes in inspiratory motoneuron output produced by in vitro neonatal rat preparations.Respiratory physiology & neurobiology · 2024Article
- Pirfenidone regulates seizures through the HMGB1/TLR4 axis to improve cognitive functions and modulate oxidative stress and neurotransmitters in PTZ-induced kindling in mice.Frontiers in pharmacology · 2024Article
- Ameliorative Potential of (-) Pseudosemiglabrin in Mice with Pilocarpine-Induced Epilepsy: Antioxidant, Anti-Inflammatory, Anti-Apoptotic, and Neurotransmission Modulation.International journal of molecular sciences · 2023Article
- Toll-Like Receptor 4 Plays a Significant Role in the Biochemical and Neurological Alterations Observed in Two Distinct Mice Models of Huntington's Disease.Molecular neurobiology · 2023Article
- Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain.Neural regeneration research · 2023Review
- Review
- Protective Effect of Ulinastatin on Cognitive Function After Hypoxia.Neuromolecular medicine · 2023Article
- Synapse Dysfunctions in Multiple Sclerosis.International journal of molecular sciences · 2023Review
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Toll like receptor 4 (TLR4) is an innate immune pattern recognition receptor, expressed predominantly on microglia in the CNS. Activation of spinal TLR4 plays a critical role in the genesis of pathological pain induced by nerve injury, bone cancer, and tissue inflammation. Currently, it remains unknown how synaptic activities in the spinal dorsal horn are regulated by TLR4 receptors. Through recording GABAergic currents in neurons and glial glutamate transporter currents in astrocytes in rodent spinal slices, we determined whether and how TLR4 modulates GABAergic synaptic activities in the superficial spinal dorsal horn. We found that activation of TLR4 by lipopolysaccharide (LPS) reduces GABAergic synaptic activities through both presynaptic and postsynaptic mechanisms. Specifically, LPS causes the release of IL-1β from microglia. IL-1β in turn suppresses GABA receptor activities at the postsynaptic site through activating protein kinase C (PKC) in neurons. GABA synthesis at the presynaptic site is reduced upon activation of TLR4. Glial glutamate transporter activities are suppressed by IL-1β and PKC activation induced by LPS. The suppression of glial glutamate transporter activities leads to a deficiency of glutamine supply, which results in an attenuation of the glutamate-glutamine cycle-dependent GABA synthesis. These findings shed light on understanding synaptic plasticity induced by activation of TLR4 under neuroinflammation and identify GABA receptors, glial glutamate transporters, IL-1β and PKC as therapeutic targets to abrogate abnormal neuronal activities following activation of TLR4 in pathological pain conditions.
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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.