ArticleEpilepsia2014
Antiseizure effects of TrkB kinase inhibition.
Article in Epilepsia, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 13 papers.
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Who cites it
13 citing papers in PubMed, 27 citations in OpenAlex.
- Different mechanisms of axitinib and diazepam antiseizure action in pentylenetetrazol-induced kindling model.IBRO neuroscience reports · 2025Article
- The Intricate Relationship of Trk Receptors in Brain Diseases and Disorders.Molecular neurobiology · 2025Review
- Functional characterization and potential therapeutic avenues for variants in the NTRK2 gene causing developmental and epileptic encephalopathies.American journal of medical genetics. Part B, Neuropsychiatric genetics : the official publication of the International Society of Psychiatric Genetics · 2022Article
- The Role of Brain-Derived Neurotrophic Factor in Epileptogenesis: an Update.Frontiers in pharmacology · 2021Review
- Astrocytic BDNF and TrkB regulate severity and neuronal activity in mouse models of temporal lobe epilepsy.Cell death & disease · 2020Article
- Epilepsy-on-a-Chip System for Antiepileptic Drug Discovery.IEEE transactions on bio-medical engineering · 2019Article
- Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation.Molecular neurobiology · 2019Review
- Cortistatin-expressing interneurons require TrkB signaling to suppress neural hyper-excitability.Brain structure & function · 2019Article
- The Role of Altered BDNF/TrkB Signaling in Amyotrophic Lateral Sclerosis.Frontiers in cellular neuroscience · 2019Review
- Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity.Scientific reports · 2016Article
- Analysis of rare copy number variation in absence epilepsies.Neurology. Genetics · 2016Article
- Epigenetics of Epileptogenesis-Evoked Upregulation of Matrix Metalloproteinase-9 in Hippocampus.PloS one · 2016Article
- Neurotrophin receptors expression in mesial temporal lobe epilepsy with and without psychiatric comorbidities and their relation with seizure type and surgical outcome.Acta neuropathologica communications · 2014Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
objectiveThe principal molecular targets of conventional antiseizure drugs consist of ligand-gated and voltage-gated ion channels and proteins subserving synaptic function. Inhibition of the receptor tyrosine kinase TrkB limits epileptogenesis, but its effect on individual seizures is unknown. We sought to determine whether inhibition of TrkB kinase exerts an antiseizure effect.
methodsWe utilized the kindling model in combination with an inducible conditional knockout of the TrkB gene (Act-CreER TrkB(flox/flox) mice treated with tamoxifen), and also with a chemical-genetic approach in which mice carry a TrkB kinase with a phenylalanine to alanine substitution of residue 616 (TrkB(F) (616A) ), which allows inhibition of the kinase by a blood-brain barrier permeable small molecule, 1'-naphthylmethyl-4-amino-1-tert-butyl-3-(p-methylphenyl)pyrazolo[3,4-d]pyrimidine (1NMPP1).
resultsFollowing induction of kindling, reduction of TrkB protein levels in Act-CreER TrkB(flox/flox) mice treated with tamoxifen was associated with reduced severity of behavioral seizures evoked by stimulation. Treatment with 1NMPP1 for 2 weeks following induction of kindling reversibly elevated both focal electrographic and generalized seizure thresholds in TrkB(F) (616A) , but not wild-type (WT), mice. In contrast to kindled animals, treatment of naive TrkB(F) (616A) mice for 2 weeks had no detectable effect on electrographic seizure threshold (EST). SIGNIFICANCE: This study provides proof of concept of a novel molecular target for antiseizure drugs, namely the receptor tyrosine kinase TrkB.
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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.