ArticleMolecular neurobiology2016
Gephyrin Cleavage in In Vitro Brain Ischemia Decreases GABAA Receptor Clustering and Contributes to Neuronal Death.
Article in Molecular neurobiology, 2016. 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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30 citing papers in PubMed, 47 citations in OpenAlex.
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- Restoration of Extrasynaptic/Synaptic GABANeuroscience bulletin · 2026Article
- Activation of the 20S proteasome core particle prevents cell death induced by oxygen- and glucose deprivation in cultured cortical neurons.Apoptosis : an international journal on programmed cell death · 2025Article
- Chronic benzodiazepine treatment triggers gephyrin scaffold destabilization and GABAFrontiers in cellular neuroscience · 2025Article
- TRPM2 and CaMKII Signaling Drives Excessive GABAergic Synaptic Inhibition Following Ischemia.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2024Article
- Research advances in huntingtin-associated protein 1 and its application prospects in diseases.Frontiers in neuroscience · 2024Review
- Preclinical evaluation of ZL006-05, a new antistroke drug with fast-onset antidepressant and anxiolytic effects.Stroke and vascular neurology · 2023Article
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- nNOS and Neurological, Neuropsychiatric Disorders: A 20-Year Story.Neuroscience bulletin · 2023Review
- Molecular Mechanisms of Epilepsy: The Role of the Chloride Transporter KCC2.Journal of molecular neuroscience : MN · 2022Review
- Complex regulation of Gephyrin splicing is a determinant of inhibitory postsynaptic diversity.Nature communications · 2022Article
- Spatial regulation of coordinated excitatory and inhibitory synaptic plasticity at dendritic synapses.Cell reports · 2022Article
- Crosstalk Between GABAergic Neurotransmission and Inflammatory Cascades in the Post-ischemic Brain: Relevance for Stroke Recovery.Frontiers in cellular neuroscience · 2022Review
- The Yin and Yang of GABAergic and Glutamatergic Synaptic Plasticity: Opposites in Balance by Crosstalking Mechanisms.Frontiers in synaptic neuroscience · 2022Review
- Stepwise disassembly of GABAergic synapses during pathogenic excitotoxicity.Cell reports · 2021Article
- Synergic Neuroprotection BetweenFrontiers in pharmacology · 2021Article
- Neuronal Plasticity: Neuronal Organization is Associated with Neurological Disorders.Journal of molecular neuroscience : MN · 2020Review
- Tuning GABAergic Inhibition: Gephyrin Molecular Organization and Functions.Neuroscience · 2020Review
- Calpain-dependent cleavage of GABAergic proteins during epileptogenesis.Epilepsy research · 2019Article
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Authors and funding
9 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
GABA (γ-aminobutyric acid) is the major inhibitory neurotransmitter in the central nervous system, and changes in GABAergic neurotransmission modulate the activity of neuronal networks. Gephyrin is a scaffold protein responsible for the traffic and synaptic anchoring of GABAA receptors (GABAAR); therefore, changes in gephyrin expression and oligomerization may affect the activity of GABAergic synapses. In this work, we investigated the changes in gephyrin protein levels during brain ischemia and in excitotoxic conditions, which may affect synaptic clustering of GABAAR. We found that gephyrin is cleaved by calpains following excitotoxic stimulation of hippocampal neurons with glutamate, as well as after intrahippocampal injection of kainate, giving rise to a stable cleavage product. Gephyrin cleavage was also observed in cultured hippocampal neurons subjected to transient oxygen-glucose deprivation (OGD), an in vitro model of brain ischemia, and after transient middle cerebral artery occlusion (MCAO) in mice, a model of focal brain ischemia. Furthermore, a truncated form of gephyrin decreased the synaptic clustering of the protein, reduced the synaptic pool of GABAAR containing γ2 subunits and upregulated OGD-induced cell death in hippocampal cultures. Our results show that excitotoxicity and brain ischemia downregulate full-length gephyrin with a concomitant generation of truncated products, which affect synaptic clustering of GABAAR and cell death.
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