ArticleMolecular neurobiology2016
Adult Deletion of SRF Increases Epileptogenesis and Decreases Activity-Induced Gene Expression.
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 33 papers.
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Who cites it
33 citing papers in PubMed, 73 citations in OpenAlex.
- Lithium pretreatment does not affect pilocarpine-induced seizure-like activity in zebrafish larvae.Pharmacological reports : PR · 2026Article
- Lcn2 deficiency leads to long-lasting social impairments independent of maternal immune activation.Journal of neuroinflammation · 2026Article
- SRF Facilitates Transcriptional Inhibition of Gem Expression by m6A Methyltransferase METTL3 to Suppress Neuronal Damage in Epilepsy.Molecular neurobiology · 2025Article
- Article
- Unveiling the role of histone deacetylases in neurological diseases: focus on epilepsy.Biomarker research · 2024Review
- SRF deletion results in earlier disease onset in a mouse model of amyotrophic lateral sclerosis.JCI insight · 2023Article
- SRF in Neurochemistry: Overview of Recent Advances in Research on the Nervous System.Neurochemical research · 2022Review
- SRF depletion in early life contributes to social interaction deficits in the adulthood.Cellular and molecular life sciences : CMLS · 2022Article
- Regulation of Dendritic Synaptic Morphology and Transcription by the SRF Cofactor MKL/MRTF.Frontiers in molecular neuroscience · 2021Review
- Article
- Neuronal activity regulates alternative exon usage.Molecular brain · 2020Article
- Exercise-dependent increases in protein synthesis are accompanied by chromatin modifications and increased MRTF-SRF signalling.Acta physiologica (Oxford, England) · 2020Article
- SRF and SRFΔ5 Splicing Isoform Recruit Corepressor LSD1/KDM1A Modifying Structural Neuroplasticity and Environmental Stress Response.Molecular neurobiology · 2020Article
- Inferior Colliculus Transcriptome After Status Epilepticus in the Genetically Audiogenic Seizure-Prone Hamster GASH/Sal.Frontiers in neuroscience · 2020Article
- Critical role of CRAG, a splicing variant of centaurin-γ3/AGAP3, in ELK1-dependent SRF activation at PML bodies.Scientific reports · 2019Article
- Firing Rate Homeostasis Can Occur in the Absence of Neuronal Activity-Regulated Transcription.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2019Article
- The neuronal stimulation-transcription coupling map.Current opinion in neurobiology · 2019Review
- Loss of serum response factor in mature neurons in the dentate gyrus alters the morphology of dendritic spines and hippocampus-dependent behavioral tasks.Brain structure & function · 2019Article
- Single-molecule imaging of the transcription factor SRF reveals prolonged chromatin-binding kinetics upon cell stimulation.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Article
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Although the transcription factor serum response factor (SRF) has been suggested to play a role in activity-dependent gene expression and mediate plasticity-associated structural changes in the hippocampus, no unequivocal evidence has been provided for its role in brain pathology, such as epilepsy. A genome-wide program of activity-induced genes that are regulated by SRF also remains unknown. In the present study, we show that the inducible and conditional deletion of SRF in the adult mouse hippocampus increases the epileptic phenotype in the kainic acid model of epilepsy, reflected by more severe and frequent seizures. Moreover, we observe a robust decrease in activity-induced gene transcription in SRF knockout mice. We characterize the genetic program controlled by SRF in neurons and using functional annotation, we find that SRF target genes are associated with synaptic plasticity and epilepsy. Several of these SRF targets function as regulators of inhibitory or excitatory balance and the structural plasticity of neurons. Interestingly, mutations in those SRF targets have found to be associated with such human neuropsychiatric disorders, as autism and intellectual disability. We also identify novel direct SRF targets in hippocampus: Npas4, Gadd45g, and Zfp36. Altogether, our data indicate that proteins that are highly upregulated by neuronal stimulation, identified in the present study as SRF targets, may function as endogenous protectors against overactivation. Thus, the lack of these effector proteins in SRF knockout animals may lead to uncontrolled excitation and eventually epilepsy.
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