ArticleAnnals of clinical and translational neurology2019
Effects of antiepileptic drugs in a new TSC/mTOR-dependent epilepsy mouse model.
Article in Annals of clinical and translational neurology, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed.
- Conditional Modeling of GNAO1 Disorder Dissociates Circuit Specific Contributions to Pathology and Rationalizes Ameliorative Strategies.Movement disorders : official journal of the Movement Disorder Society · 2026Article
- Altered PI3K/mTOR Signaling within the Forebrain Leads to Respiratory Deficits in a Mouse Model of Epilepsy.eNeuro · 2025Article
- Epilepsy and autophagy modulators: a therapeutic split.Autophagy · 2025Review
- Pathophysiology of Status Epilepticus Revisited.International journal of molecular sciences · 2025Review
- Impact of the Ketogenic Diet on Neurological Diseases: A Review.Life (Basel, Switzerland) · 2025Review
- Focal postnatal deletion ofFrontiers in molecular neuroscience · 2025Article
- Recent Advances in Pharmacologic Treatments of Drug-Resistant Epilepsy: Breakthrough in Sight.CNS drugs · 2024Review
- Compartment-specific small non-coding RNA changes and nucleolar defects in human mesial temporal lobe epilepsy.Acta neuropathologica · 2024Article
- A ketogenic diet enhances fluconazole efficacy in murine models of systemic fungal infection.mBio · 2024Article
- mTOR and neuroinflammation in epilepsy: implications for disease progression and treatment.Nature reviews. Neuroscience · 2024Review
- New insights on the potential anti-epileptic effect of metformin: Mechanistic pathway.Journal of cellular and molecular medicine · 2023Review
- Targeted suppression of mTORC2 reduces seizures across models of epilepsy.Nature communications · 2023Article
- Autophagy and autophagy signaling in Epilepsy: possible role of autophagy activator.Molecular medicine (Cambridge, Mass.) · 2023Review
- Epileptogenesis in tuberous sclerosis complex-related developmental and epileptic encephalopathy.Brain : a journal of neurology · 2023Review
- Advances in the mTOR signaling pathway and its inhibitor rapamycin in epilepsy.Brain and behavior · 2023Review
- Traditional and Innovative Anti-seizure Medications Targeting Key Physiopathological Mechanisms: Focus on Neurodevelopment and Neurodegeneration.Current neuropharmacology · 2023Article
- Expression of 4E-BP1 in juvenile mice alleviates mTOR-induced neuronal dysfunction and epilepsy.Brain : a journal of neurology · 2022Article
- Insights into the Cellular Interactions and Molecular Mechanisms of Ketogenic Diet for Comprehensive Management of Epilepsy.Current neuropharmacology · 2022Review
- Article
- Identifying the temporal electrophysiological and molecular changes that contribute to TSC-associated epileptogenesis.JCI insight · 2021Article
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Authors and funding
8 authors.
Funding
Abstract
objectiveAn epilepsy mouse model for Tuberous Sclerosis Complex (TSC) was developed and validated to investigate the mechanisms underlying epileptogenesis. Furthermore, the possible antiepileptogenic properties of commonly used antiepileptic drugs (AEDs) and new compounds were assessed.
methodsTsc1 deletion was induced in CAMK2A-expressing neurons of adult mice. The antiepileptogenic properties of commonly used AEDs and inhibitors of the mTOR pathways were assessed by EEG recordings and by molecular read outs.
resultsMice developed epilepsy in a narrow time window (10 ± 2 days) upon Tsc1 gene deletion. Seizure frequency but not duration increased over time. Seizures were lethal within 18 days, were unpredictable, and did not correlate to seizure onset, length or frequency, reminiscent of sudden unexpected death in epilepsy (SUDEP). Tsc1 gene deletion resulted in a strong activation of the mTORC1 pathway, and both epileptogenesis and lethality could be entirely prevented by RHEB1 gene deletion or rapamycin treatment. However, other inhibitors of the mTOR pathway such as AZD8055 and PF4708671 were ineffective. Except for ketogenic diet, none of commonly used AEDs showed an effect on mTORC1 activity. Vigabatrin and ketogenic diet treatment were able to significantly delay seizure onset. In contrast, survival was shortened by lamotrigine.
interpretationThis novel Tsc1 mouse model is highly suitable to assess the efficacy of antiepileptic and -epileptogenic drugs to treat mTORC1-dependent epilepsy. Additionally, it allows us to study the mechanisms underlying mTORC1-mediated epileptogenesis and SUDEP. We found that early treatment with vigabatrin was not able to prevent epilepsy, but significantly delayed seizure onset.
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