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Updated: Feb 3, 2026
08:48
Synaptic Microcircuit Modeling with 3D Cocultures of Astrocytes and Neurons from Human Pluripotent Stem Cells
Published on: August 16, 2018
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Blocking TNFα-driven astrocyte purinergic signaling restores normal synaptic activity during epileptogenesis
Ljiljana Nikolic1, Weida Shen1,2, Paola Nobili1
1Neuron-glia interactions group, INSERM U1128, Paris Descartes University, Paris, France.
Glia
|November 6, 2018
Summary
Tumor necrosis factor alpha (TNFα) drives abnormal glutamate release from astrocytes in epilepsy via purinergic signaling. Blocking this pathway with P2Y1 receptor inhibitors normalizes brain activity, offering a potential epilepsy treatment.
Area of Science:
- Neuroscience
- Cellular and Molecular Biology
- Epilepsy Research
Background:
- Epilepsy involves recurrent seizures due to neuronal hyperexcitability.
- Aberrant astrocyte signaling contributes to epilepsy, but mechanisms are unclear.
- Tumor necrosis factor alpha (TNFα) influences astrocyte glutamate release.
Purpose of the Study:
- Investigate if TNFα controls abnormal astrocyte glutamate signaling in epilepsy.
- Elucidate the mechanism by which TNFα alters glial signaling.
Main Methods:
- Calcium (Ca2+) imaging
- Optogenetics
- Electrophysiology
- Mouse model of temporal lobe epilepsy
Main Results:
- TNFα induces Ca2+-dependent glutamate release from astrocytes.
- This release enhances hippocampal excitatory synaptic activity via P2Y1 receptor activation.
- In epilepsy models, this TNFα-driven purinergic signaling is persistently active, promoting seizures.
- Inhibition of P2Y1 receptors restores normal synaptic activity.
Conclusions:
- TNFα couples with astrocyte purinergic signaling to drive glutamate release in epilepsy.
- Targeting this TNFα-astrocyte pathway offers a potential therapeutic strategy for epilepsy.
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