ArticleThe Journal of cell biology2016
Postnatal activation of TLR4 in astrocytes promotes excitatory synaptogenesis in hippocampal neurons.
Article in The Journal of cell biology, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 75 papers.
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Who cites it
75 citing papers in PubMed, 131 citations in OpenAlex.
- Orexin-A Inhibits Lipopolysaccharide-Induced Cell Migration in Cultured Mouse Astrocytes via Activation of Orexin 1 Receptor: Involvement of GABA Signaling.Journal of cellular biochemistry · 2026Article
- BTP2, a store-operated calcium channel inhibitor, attenuates morphine antinociceptive tolerance in rats.Frontiers in neuroscience · 2026Article
- APOE-Glia Crosstalk in Epilepsy: Mechanisms, Controversies, and Therapeutic Perspectives.Journal of inflammation research · 2026Review
- Microglial activation drives neuronal dysregulation in alcohol-induced seizure susceptibility.Scientific reports · 2025Article
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- Arteries and veins in awake mice using two-photon microscopy.Journal of anatomy · 2025Article
- Glycogenolysis-Induced Astrocytic Serping1 Expression Regulates Neuroinflammatory Effects on Hippocampal neuron.Molecular neurobiology · 2025Article
- Silencing epileptic storms: targeting miRNA-lncRNA crosstalk in astrocytes and microglia to disarm neuroinflammatory triggers.Frontiers in molecular neuroscience · 2025Review
- Early Postnatal Neuroinflammation Produces Key Features of Diffuse Brain White Matter Injury in Rats.Brain sciences · 2024Article
- Microglia in neuroimmunopharmacology and drug addiction.Molecular psychiatry · 2024Review
- From Immunity to Neurogenesis: Toll-like Receptors as Versatile Regulators in the Nervous System.International journal of molecular sciences · 2024Review
- Neuroactive Steroids, Toll-like Receptors, and Neuroimmune Regulation: Insights into Their Impact on Neuropsychiatric Disorders.Life (Basel, Switzerland) · 2024Review
- Characterization of Retinal VIP-Amacrine Cell Development During the Critical Period.Cellular and molecular neurobiology · 2024Article
- Toll-Like Receptor 4 Deficiency Ameliorates Propofol-Induced Impairments of Cognitive Function and Synaptic Plasticity in Young Mice.Molecular neurobiology · 2024Article
- Recent Developments and Application of Mass Spectrometry Imaging in N-Glycosylation Studies: An Overview.Mass spectrometry (Tokyo, Japan) · 2024Review
- A novel combination treatment for fragile X syndrome predicted using computational methods.Brain communications · 2024Article
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- ROS-removing nano-medicine for navigating inflammatory microenvironment to enhance anti-epileptic therapy.Acta pharmaceutica Sinica. B · 2023Article
15 more citing papers are in PubMed but not listed here.
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Authors and funding
11 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Astrocytes are critical in synapse development, and their dysfunction in crucial developmental stages leads to serious neurodevelopmental diseases, including seizures and epilepsy. Immune challenges not only affect brain development, but also promote seizure generation and epileptogenesis, implying immune activation is one of the key factors linking seizures and epilepsy to abnormal brain development. In this study, we report that activating astrocytes by systemic lipopolysaccharide (LPS) challenges in the second postnatal week promotes excitatory synapse development, leading to enhanced seizure susceptibility in mice. Toll-like receptor 4 (TLR4) activation in astrocytes increased astrocytic extracellular signal-related kinase 1/2 (Erk1/2) and phospho-Erk1/2 levels in a myeloid differentiation primary response protein 88 (MyD88)-dependent manner. Constitutively activating Erk1/2 in astrocytes was sufficient to enhance excitatory synaptogenesis without activating TLR4. Deleting MyD88 or suppressing Erk1/2 in astrocytes rescued LPS-induced developmental abnormalities of excitatory synapses and restored the enhanced seizure sensitivity. Thus, we provide direct evidence for a developmental role of astrocytes in shaping a predisposition to seizure generation.
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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.