ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Inhibition of the mammalian target of rapamycin signaling pathway suppresses dentate granule cell axon sprouting in a rodent model of temporal lobe epilepsy.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 135 papers.
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Who cites it
135 citing papers in PubMed, 226 citations in OpenAlex.
- Advancing the Paradigm of Temporal Lobe Epilepsy as a Network Disease: The Promise of Biomarkers and Targeted Disease Modification.International journal of molecular sciences · 2026Review
- Rapamycin and Minocycline Treatment Does Not Rescue Behavioral and Molecular Changes Induced by Early-Life Seizures in Female Mice.NeuroSci · 2026Article
- Cell-Intrinsic Regulation of Epilepsy-Associated Pathology by mTORC1 and mTORC2.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2026Article
- The Role of HIF-1α/BNIP3 Pathway in Hippocampal Neuronal Autophagy in Epilepsy.Molecular neurobiology · 2025Article
- Pathophysiology of Status Epilepticus Revisited.International journal of molecular sciences · 2025Review
- Article
- Resveratrol: A Natural Compound Targeting the PI3K/Akt/mTOR Pathway in Neurological Diseases.Molecular neurobiology · 2025Review
- Erythropoietin for Seizures and Epilepsy: Neuroprotective Effects, Mechanisms, and Contradictory Risks.CNS & neurological disorders drug targets · 2025Review
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
- Chronic Epilepsy and Mossy Fiber Sprouting Following Organophosphate-Induced Status Epilepticus in Rats.The Journal of pharmacology and experimental therapeutics · 2024Article
- Zinc Oxide Nanoparticles Exacerbate Epileptic Seizures by Modulating the TLR4-Autophagy Axis.International journal of nanomedicine · 2024Article
- Emerging Molecular Targets for Anti-Epileptogenic and Epilepsy Modifying Drugs.International journal of molecular sciences · 2023Review
- IDH-mutated gliomas promote epileptogenesis through d-2-hydroxyglutarate-dependent mTOR hyperactivation.Neuro-oncology · 2022Article
- DEPDC5-dependent mTORC1 signaling mechanisms are critical for the anti-seizure effects of acute fasting.Cell reports · 2022Article
- Adenosine AScientific reports · 2022Article
- Review
- Post-Traumatic Epilepsy and Comorbidities: Advanced Models, Molecular Mechanisms, Biomarkers, and Novel Therapeutic Interventions.Pharmacological reviews · 2022Review
- The role of mTORC1 activation in seizure-induced exacerbation of Alzheimer's disease.Brain : a journal of neurology · 2022Article
- Rapamycin, but not minocycline, significantly alters ultrasonic vocalization behavior in C57BL/6J pups in a flurothyl seizure model.Behavioural brain research · 2021Article
- Astrocyte Role in Temporal Lobe Epilepsy and Development of Mossy Fiber Sprouting.Frontiers in cellular neuroscience · 2021Review
75 more citing papers are in PubMed but not listed here.
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Dentate granule cell axon (mossy fiber) sprouting is a common abnormality in patients with temporal lobe epilepsy. Mossy fiber sprouting creates an aberrant positive-feedback network among granule cells that does not normally exist. Its role in epileptogenesis is unclear and controversial. If it were possible to block mossy fiber sprouting from developing after epileptogenic treatments, its potential role in the pathogenesis of epilepsy could be tested. Previous attempts to block mossy fiber sprouting have been unsuccessful. The present study targeted the mammalian target of rapamycin (mTOR) signaling pathway, which regulates cell growth and is blocked by rapamycin. Rapamycin was focally, continuously, and unilaterally infused into the dorsal hippocampus for prolonged periods beginning within hours after rats sustained pilocarpine-induced status epilepticus. Infusion for 1 month reduced aberrant Timm staining (a marker of mossy fibers) in the granule cell layer and molecular layer. Infusion for 2 months inhibited mossy fiber sprouting more. However, after rapamycin infusion ceased, aberrant Timm staining developed and approached untreated levels. When onset of infusion began after mossy fiber sprouting had developed for 2 months, rapamycin did not reverse aberrant Timm staining. These findings suggest that inhibition of the mTOR signaling pathway suppressed development of mossy fiber sprouting. However, suppression required continual treatment, and rapamycin treatment did not reverse already established axon reorganization.
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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.