ArticleJournal of neuroinflammation2023
Cell-specific NFIA upregulation promotes epileptogenesis by TRPV4-mediated astrocyte reactivity.
Article in Journal of neuroinflammation, 2023. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 23 citations in OpenAlex.
- Glymphatic system dysfunction: a link between sleep disorders and neurodegeneration.Psychopharmacology · 2026Review
- Inhibition of endocannabinoid degradation in astrocytes reprograms glial reactivity and prevents seizure sequelae.Journal of neuroinflammation · 2026Article
- Excitatory neurons and astrocytes-specific dysregulation and aberrant interactions are vulnerable to FCDI as suggested by single-cell spatial transcriptomics.Clinical and translational medicine · 2026Article
- TRPV4 is involved in NLRP3 and NLRP1 inflammasomes activation after pilocarpine-induced status epilepticus in mice : Concise title: TRPV4-mediated inflammasome activation in epilepsy.Cellular and molecular life sciences : CMLS · 2026Article
- Early-life inflammation increases aggressive behavior in adult male mice through an astrocyte-neuron signaling.Molecular psychiatry · 2026Article
- Article
- Transient Receptor Potential Channels as Key Regulators of Neuroinflammation in Neurological Disorders: Mechanistic Insights, Therapeutic Potentials, and Future Directions.CNS neuroscience & therapeutics · 2025Review
- Single-cell transcriptomics identifies altered neutrophil dynamics and accentuated T-cell cytotoxicity in tobacco flavored e-cigarette exposed mouse lungs.bioRxiv : the preprint server for biology · 2025Article
- Calcium Signaling in Astrocytes and Its Role in the Central Nervous System Injury.Molecular neurobiology · 2025Review
- Generation of human induced pluripotent stem cell lines derived from a patient carrying an intragenic deletion in the NFIA gene.Human cell · 2025Article
- TRPV4 Channel in Neurological Disease: from Molecular Mechanisms to Therapeutic Potential.Molecular neurobiology · 2025Review
- Understanding Headaches Attributed to Cranial and/or Cervical Vascular Disorders: Insights and Challenges for Neurologists.Pain and therapy · 2024Review
- Seizures Triggered by Systemic Administration of 4-Aminopyridine in Rats Lead to Acute Brain Glucose Hypometabolism, as Assessed by [International journal of molecular sciences · 2024Article
- Role of inflammatory cytokine in mediating the effect of plasma lipidome on epilepsy: a mediation Mendelian randomization study.Frontiers in neurology · 2024Article
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Authors and funding
14 authors at 3 institutions in 1 country.
Funding
Abstract
backgroundThe astrocytes in the central nervous system (CNS) exhibit morphological and functional diversity in brain region-specific pattern. Functional alterations of reactive astrocytes are commonly present in human temporal lobe epilepsy (TLE) cases, meanwhile the neuroinflammation mediated by reactive astrocytes may advance the development of hippocampal epilepsy in animal models. Nuclear factor I-A (NFIA) may regulate astrocyte diversity in the adult brain. However, whether NFIA endows the astrocytes with regional specificity to be involved in epileptogenesis remains elusive.
methodsHere, we utilize an interference RNA targeting NFIA to explore the characteristics of NFIA expression and its role in astrocyte reactivity in a 4-aminopyridine (4-AP)-induced seizure model in vivo and in vitro. Combined with the employment of a HA-tagged plasmid overexpressing NFIA, we further investigate the precise mechanisms how NIFA facilitates epileptogenesis.
results4-AP-induced NFIA upregulation in hippocampal region is astrocyte-specific, and primarily promotes detrimental actions of reactive astrocyte. In line with this phenomenon, both NFIA and vanilloid transient receptor potential 4 (TRPV4) are upregulated in hippocampal astrocytes in human samples from the TLE surgical patients and mouse samples with intraperitoneal 4-AP. NFIA directly regulates mouse astrocytic TRPV4 expression while the quantity and the functional activity of TRPV4 are required for 4-AP-induced astrocyte reactivity and release of proinflammatory cytokines in the charge of NFIA upregulation. NFIA deficiency efficiently inhibits 4-AP-induced TRPV4 upregulation, weakens astrocytic calcium activity and specific astrocyte reactivity, thereby mitigating aberrant neuronal discharges and neuronal damage, and suppressing epileptic seizure.
conclusionsOur results uncover the critical role of NFIA in astrocyte reactivity and illustrate how epileptogenic brain injury initiates cell-specific signaling pathway to dictate the astrocyte responses.
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