ArticleMolecular brain2016
Feedback modulation of neural network synchrony and seizure susceptibility by Mdm2-p53-Nedd4-2 signaling.
Article in Molecular brain, 2016. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 25 papers.
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Who cites it
25 citing papers in PubMed, 36 citations in OpenAlex.
- Neuronal Activity Rapidly Decreases the Level of p53 Protein in Rat Hippocampus In Vivo.Bulletin of experimental biology and medicine · 2026Article
- A novel lncRNA, lncMCL1, modulates neural pyroptosis associated with epilepsy via stabilizing DDX3X.Cell death and differentiation · 2026Article
- Histone variant H2BE controls activity-dependent gene expression and homeostatic scaling.Cell reports · 2026Article
- mGluR7 allosteric modulator AMN082 corrects protein synthesis and pathological phenotypes in FXS.EMBO molecular medicine · 2024Article
- Hyperfunction of post-synaptic density protein 95 promotes seizure response in early-stage aβ pathology.EMBO reports · 2024Article
- Pentylenetetrazole-Induced Seizures Are Increased after Kindling, Exhibiting Vitamin-Responsive Correlations to the Post-Seizures Behavior, Amino Acids Metabolism and Key Metabolic Regulators in the Rat Brain.International journal of molecular sciences · 2023Article
- PLEKHM2 Loss of Function Impairs the Activity of iPSC-Derived Neurons via Regulation of Autophagic Flux.International journal of molecular sciences · 2022Article
- E3 ubiquitin ligase NEDD4L negatively regulates inflammation by promoting ubiquitination of MEKK2.EMBO reports · 2022Article
- Transcription factors are potential therapeutic targets in epilepsy.Journal of cellular and molecular medicine · 2022Review
- Amyloid beta induces Fmr1-dependent translational suppression and hyposynchrony of neural activity via phosphorylation of eIF2α and eEF2.Journal of cellular physiology · 2022Article
- Genetic Deficiency of p53 Leads to Structural, Functional, and Synaptic Deficits in Primary Somatosensory Cortical Neurons of Adult Mice.Frontiers in molecular neuroscience · 2022Article
- ER stress-induced modulation of neural activity and seizure susceptibility is impaired in a fragile X syndrome mouse model.Neurobiology of disease · 2021Article
- Beraprost ameliorates postmenopausal osteoporosis by regulating Nedd4-induced Runx2 ubiquitination.Cell death & disease · 2021Article
- PLPP/CIN-mediated NF2-serine 10 dephosphorylation regulates F-actin stability and Mdm2 degradation in an activity-dependent manner.Cell death & disease · 2021Article
- Neurodegenerative pathways as targets for acquired epilepsy therapy development.Epilepsia open · 2020Review
- Novel roles of ER stress in repressing neural activity and seizures through Mdm2- and p53-dependent protein translation.PLoS genetics · 2019Article
- PLPP/CIN-mediated NEDD4-2 S448 dephosphorylation regulates neuronal excitability via GluA1 ubiquitination.Cell death & disease · 2019Article
- Optimization of makerspace microfabrication techniques and materials for the realization of planar, 3D printed microelectrode arrays in under four days.RSC advances · 2019Article
- Dysregulation and restoration of homeostatic network plasticity in fragile X syndrome mice.Neuropharmacology · 2018Article
- Mdm2 mediates FMRP- and Gp1 mGluR-dependent protein translation and neural network activity.Human molecular genetics · 2017Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundNeural network synchrony is a critical factor in regulating information transmission through the nervous system. Improperly regulated neural network synchrony is implicated in pathophysiological conditions such as epilepsy. Despite the awareness of its importance, the molecular signaling underlying the regulation of neural network synchrony, especially after stimulation, remains largely unknown.
resultsIn this study, we show that elevation of neuronal activity by the GABA(A) receptor antagonist, Picrotoxin, increases neural network synchrony in primary mouse cortical neuron cultures. The elevation of neuronal activity triggers Mdm2-dependent degradation of the tumor suppressor p53. We show here that blocking the degradation of p53 further enhances Picrotoxin-induced neural network synchrony, while promoting the inhibition of p53 with a p53 inhibitor reduces Picrotoxin-induced neural network synchrony. These data suggest that Mdm2-p53 signaling mediates a feedback mechanism to fine-tune neural network synchrony after activity stimulation. Furthermore, genetically reducing the expression of a direct target gene of p53, Nedd4-2, elevates neural network synchrony basally and occludes the effect of Picrotoxin. Finally, using a kainic acid-induced seizure model in mice, we show that alterations of Mdm2-p53-Nedd4-2 signaling affect seizure susceptibility.
conclusionTogether, our findings elucidate a critical role of Mdm2-p53-Nedd4-2 signaling underlying the regulation of neural network synchrony and seizure susceptibility and reveal potential therapeutic targets for hyperexcitability-associated neurological disorders.
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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.