ArticleProceedings of the National Academy of Sciences of the United States of America2021
Astrocyte-secreted IL-33 mediates homeostatic synaptic plasticity in the adult hippocampus.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers, 1 of them a synthesis that pooled it.
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Who cites it
77 citing papers in PubMed, 1 synthesis or guideline pooled it, 130 citations in OpenAlex.
- The role of IL-33 in depression: a systematic review and meta-analysis.Frontiers in psychiatry · 2023Pooled it
- IL-33 as a boundary-tissue state-transfer signal: a Reader-Alarmin-Effector architecture linking CNS and skin.Brain, behavior, & immunity - health · 2026Review
- FMRP Regulates NrCAM Expression via β-catenin and Modulates PSD95, Dendritic Spines and Autism-like Behaviors.Neuroscience bulletin · 2026Article
- TNF-dependent regulation of synaptic plasticity and neuronal activity: implications for psychiatric disorders.Molecular psychiatry · 2026Review
- Sex differences in the effects of chronic stress and oxycodone associative learning on glial markers in rat hippocampus.Neuroscience · 2026Article
- Article
- Repurposing trazodone for Alzheimer's disease to modulate soluble ST2 levels and alleviate Alzheimer's pathology.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Metabolic crosstalk in the ageing brain: astrocyte-neuron coupling as a target for homeostatic restoration and therapy.Translational neurodegeneration · 2026Review
- Astrocyte-driven multicellular mechanisms of CNS repair and cerebroprotection.Journal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2026Review
- Astrocyte-specific NRCAM deficiency promotes GABAergic synapse pruning to drive central sensitization in bone cancer pain.Journal of translational medicine · 2026Article
- IL-33-induced neuroimmune regulation in depression: A narrative review from molecular mechanisms to therapeutic potential.Medicine · 2026Review
- Circular RNAScience advances · 2026Article
- Article
- Advances in cellular and molecular mechanisms of trauma-induced organ inflammation and dysfunction.Burns & trauma · 2026Review
- Predictive roles of serum IL-33/ST2 and BDNF in depressed patients with repetitive transcranial magnetic stimulation: a pilot study.Frontiers in human neuroscience · 2026Article
- Tuina Inhibits Synaptic Plasticity Through the Astrocytic NDRG2/GLT-1 Pathway to Alleviate Neuropathic Pain.Journal of cellular and molecular medicine · 2026Article
- Insulin and IGF signaling in the brain: multilevel regulation of synaptic and network homeostasis.Frontiers in endocrinology · 2026Review
- Astrocytic SIRT1 ameliorates cognitive deficits after traumatic brain injury via autophagy-mediated MEGF10 phagocytosis.Journal of neuroinflammation · 2025Article
- Alcohol dependence-induced astrocyte immune activation in the nucleus accumbens.Neurobiology of disease · 2025Article
- Spatiotemporal Immune Dynamics in Experimental Retinal Ganglion Cell Injury Models.Immunity, inflammation and disease · 2025Review
17 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Hippocampal synaptic plasticity is important for learning and memory formation. Homeostatic synaptic plasticity is a specific form of synaptic plasticity that is induced upon prolonged changes in neuronal activity to maintain network homeostasis. While astrocytes are important regulators of synaptic transmission and plasticity, it is largely unclear how they interact with neurons to regulate synaptic plasticity at the circuit level. Here, we show that neuronal activity blockade selectively increases the expression and secretion of IL-33 (interleukin-33) by astrocytes in the hippocampal cornu ammonis 1 (CA1) subregion. This IL-33 stimulates an increase in excitatory synapses and neurotransmission through the activation of neuronal IL-33 receptor complex and synaptic recruitment of the scaffold protein PSD-95. We found that acute administration of tetrodotoxin in hippocampal slices or inhibition of hippocampal CA1 excitatory neurons by optogenetic manipulation increases IL-33 expression in CA1 astrocytes. Furthermore, IL-33 administration in vivo promotes the formation of functional excitatory synapses in hippocampal CA1 neurons, whereas conditional knockout of IL-33 in CA1 astrocytes decreases the number of excitatory synapses therein. Importantly, blockade of IL-33 and its receptor signaling in vivo by intracerebroventricular administration of its decoy receptor inhibits homeostatic synaptic plasticity in CA1 pyramidal neurons and impairs spatial memory formation in mice. These results collectively reveal an important role of astrocytic IL-33 in mediating the negative-feedback signaling mechanism in homeostatic synaptic plasticity, providing insights into how astrocytes maintain hippocampal network homeostasis.
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