ArticleThe Journal of biological chemistry2008
Interleukin-1beta-dependent signaling between astrocytes and neurons depends critically on astrocytic calcineurin/NFAT activity.
Article in The Journal of biological chemistry, 2008. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 87 papers, 1 of them a synthesis that pooled it.
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Who cites it
87 citing papers in PubMed, 1 synthesis or guideline pooled it, 139 citations in OpenAlex.
- Parallel electrophysiological abnormalities due to COVID-19 infection and to Alzheimer's disease and related dementia.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2024Pooled it
- Astrocytes in maintaining neuronal health and brain function: interplay of aging, diet, and environment.Metabolic brain disease · 2025Review
- Altered Lipid Metabolism in CNS Demyelination and Remyelination Are Key Elements Driving Progressive MS.International journal of molecular sciences · 2025Review
- Inhibition of astrocyte signaling leads to sex-specific changes in microglia phenotypes in a diet-based model of cerebral small vessel disease.Journal of neuroinflammation · 2025Article
- Calcineurin inhibition may prevent Alzheimer disease in people with Down syndrome.Alzheimer's & dementia : the journal of the Alzheimer's Association · 2025Review
- Systemic determinants of brain health in ageing.Nature reviews. Neurology · 2024Review
- Oxidative stress-mediated neuroinflammation in Alzheimer's disease.Naunyn-Schmiedeberg's archives of pharmacology · 2024Review
- Inflammasomes at the crossroads of traumatic brain injury and post-traumatic epilepsy.Journal of neuroinflammation · 2024Review
- The protective role of carnosine against type 2 diabetes-induced cognitive impairment.Food science & nutrition · 2024Review
- Development of a monoclonal antibody specific for a calpain-generated ∆48 kDa calcineurin fragment, a marker of distressed astrocytes.Journal of neuroscience methods · 2024Article
- Calcineurin inhibition prevents synaptic plasticity deficit induced by brain-derived tau oligomers.Brain communications · 2024Article
- Inflammation subsequent to mild iron excess differentially alters regional brain iron metabolism, oxidation and neuroinflammation status in mice.Frontiers in aging neuroscience · 2024Article
- Mitophagy-associated programmed neuronal death and neuroinflammation.Frontiers in immunology · 2024Review
- Targeting Astrocyte Signaling Alleviates Cerebrovascular and Synaptic Function Deficits in a Diet-Based Mouse Model of Small Cerebral Vessel Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- Glial Cultures Differentiated from iPSCs of Patients withInternational journal of molecular sciences · 2023Article
- Targeting CaN/NFAT in Alzheimer's brain degeneration.Frontiers in immunology · 2023Review
- Article
- Nuclear factor of activated T-cells (NFAT) regulation of IL-1β-induced retinal vascular inflammation.Biochimica et biophysica acta. Molecular basis of disease · 2021Article
- Microglia and Astrocytes in Alzheimer's Disease in the Context of the Aberrant Copper Homeostasis Hypothesis.Biomolecules · 2021Review
- Reactive astrocytes: The nexus of pathological and clinical hallmarks of Alzheimer's disease.Ageing research reviews · 2021Review
27 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
7 authors at 1 institution in 2 countries.
Funding
Abstract
Interleukin-1beta (IL-1beta) and the Ca(2+)/calmodulin-dependent protein phosphatase, calcineurin, have each been shown to play an important role in neuroinflammation. However, whether these signaling molecules interact to coordinate immune/inflammatory processes and neurodegeneration has not been investigated. Here, we show that exogenous application of IL-1beta (10 ng/ml) recruited calcineurin/NFAT (nuclear factor of activated T cells) activation in primary astrocyte-enriched cultures within minutes, through a pathway involving IL-1 receptors and L-type Ca(2+) channels. Adenovirus-mediated delivery of the NFAT inhibitor, VIVIT, suppressed the IL-1beta-dependent induction of several inflammatory mediators and/or markers of astrocyte activation, including tumor necrosis factor alpha, granulocyte/macrophage colony-stimulating factor, and vimentin. Expression of an activated form of calcineurin in one set of astrocyte cultures also triggered the release of factors that, in turn, stimulated NFAT activity in a second set of "naive" astrocytes. This effect was prevented when calcineurin-expressing cultures co-expressed VIVIT, suggesting that the calcineurin/NFAT pathway coordinates positive feedback signaling between astrocytes. In the presence of astrocytes and neurons, 48-h delivery of IL-1beta was associated with several excitotoxic effects, including NMDA receptor-dependent neuronal death, elevated extracellular glutamate, and hyperexcitable synaptic activity. Each of these effects were reversed or ameliorated by targeted delivery of VIVIT to astrocytes. IL-1beta also caused an NFAT-dependent reduction in excitatory amino acid transporter levels, indicating a possible mechanism for IL-1beta-mediated excitotoxicity. Taken together, the results have potentially important implications for the propagation and maintenance of neuroinflammatory signaling processes associated with many neurodegenerative conditions and diseases.
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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.