ArticleJournal of neuroinflammation2012
Adenosine A2B receptor-mediated leukemia inhibitory factor release from astrocytes protects cortical neurons against excitotoxicity.
Article in Journal of neuroinflammation, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
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Who cites it
30 citing papers in PubMed, 50 citations in OpenAlex.
- Small Extracellular Vesicles from Neural Cells: Physiological and Pathological Roles, and Potential in Neurodegenerative Therapy.Advanced healthcare materials · 2026Review
- Multi-Omic Analysis of Glutamate Excitotoxicity in Primary Neuronal Cultures.Journal of neurochemistry · 2025Article
- Activation of Bradykinin BInternational journal of molecular sciences · 2024Article
- An Integrative Approach to the Current Treatment of HIV-Associated Neurocognitive Disorders and the Implementation of Leukemia Inhibitor Factor as a Mediator of Neurocognitive Preservation.Life (Basel, Switzerland) · 2023Review
- The astrocytic TRPA1 channel mediates an intrinsic protective response to vascular cognitive impairment via LIF production.Science advances · 2023Article
- A Pattern to Link Adenosine Signaling, Circadian System, and Potential Final Common Pathway in the Pathogenesis of Major Depressive Disorder.Molecular neurobiology · 2022Review
- Enteric glial adenosine 2B receptor signaling mediates persistent epithelial barrier dysfunction following acute DSS colitis.Mucosal immunology · 2022Article
- β-micrustoxin (Mlx-9), a PLAThe journal of venomous animals and toxins including tropical diseases · 2022Article
- Article
- Astrocyte-Derived Extracellular Vesicles (ADEVs): Deciphering their Influences in Aging.Aging and disease · 2021Review
- Exogenous Adenosine Antagonizes Excitatory Amino Acid Toxicity in Primary Astrocytes.Cellular and molecular neurobiology · 2021Article
- Depletion of Mitochondrial Components from Extracellular Vesicles Secreted from Astrocytes in a Mouse Model of Fragile X Syndrome.International journal of molecular sciences · 2021Article
- Glial Cells Promote Myelin Formation and Elimination.Frontiers in cell and developmental biology · 2021Review
- Adenosinergic Signaling as a Key Modulator of the Glioma Microenvironment and Reactive Astrocytes.Frontiers in neuroscience · 2021Review
- 5-N-ethyl Carboxamidoadenosine Stimulates Adenosine-2b Receptor-Mediated Mitogen-Activated Protein Kinase Pathway to Improve Brain Mitochondrial Function in Amyloid Beta-Induced Cognitive Deficit Mice.Neuromolecular medicine · 2020Article
- Mesenchymal Stem Cells Attenuated Blood-Brain Barrier Disruption via Downregulation of Aquaporin-4 Expression in EAE Mice.Molecular neurobiology · 2020Article
- Neuroregenerative and protective functions of Leukemia Inhibitory Factor in perinatal hypoxic-ischemic brain injury.Experimental neurology · 2020Article
- Astrocyte-derived extracellular vesicles: Neuroreparative properties and role in the pathogenesis of neurodegenerative disorders.Journal of controlled release : official journal of the Controlled Release Society · 2020Review
- Protective Effect of Adenosine AFrontiers in pharmacology · 2020Article
- The Function of Astrocyte Mediated Extracellular Vesicles in Central Nervous System Diseases.Frontiers in cell and developmental biology · 2020Review
Corrections and comments
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Authors and funding
9 authors at 4 institutions in 3 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeuroprotective and neurotrophic properties of leukemia inhibitory factor (LIF) have been widely reported. In the central nervous system (CNS), astrocytes are the major source for LIF, expression of which is enhanced following disturbances leading to neuronal damage. How astrocytic LIF expression is regulated, however, has remained an unanswered question. Since neuronal stress is associated with production of extracellular adenosine, we investigated whether LIF expression in astrocytes was mediated through adenosine receptor signaling.
methodsMouse cortical neuronal and astrocyte cultures from wild-type and adenosine A(2B) receptor knock-out animals, as well as adenosine receptor agonists/antagonists and various enzymatic inhibitors, were used to study LIF expression and release in astrocytes. When needed, a one-way analysis of variance (ANOVA) followed by Bonferroni post-hoc test was used for statistical analysis.
resultsWe show here that glutamate-stressed cortical neurons induce LIF expression through activation of adenosine A(2B) receptor subtype in cultured astrocytes and require signaling of protein kinase C (PKC), mitogen-activated protein kinases (MAPKs: p38 and ERK1/2), and the nuclear transcription factor (NF)-κB. Moreover, LIF concentration in the supernatant in response to 5'-N-ethylcarboxamide (NECA) stimulation was directly correlated to de novo protein synthesis, suggesting that LIF release did not occur through a regulated release pathway. Immunocytochemistry experiments show that LIF-containing vesicles co-localize with clathrin and Rab11, but not with pHogrin, Chromogranin (Cg)A and CgB, suggesting that LIF might be secreted through recycling endosomes. We further show that pre-treatment with supernatants from NECA-treated astrocytes increased survival of cultured cortical neurons against glutamate, which was absent when the supernatants were pre-treated with an anti-LIF neutralizing antibody.
conclusionsAdenosine from glutamate-stressed neurons induces rapid LIF release in astrocytes. This rapid release of LIF promotes the survival of cortical neurons against excitotoxicity.
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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 OpenQuestion graph.