Transient Inhibition of TrkB Kinase after Status Epilepticus Prevents Development of Temporal Lobe Epilepsy
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Temporal lobe epilepsy is the most common and often devastating form of human epilepsy. The molecular mechanism underlying the development of temporal lobe epilepsy remains largely unknown. Emerging evidence suggests that activation of the BDNF receptor TrkB promotes epileptogenesis caused by status epilepticus. We investigated a mouse model in which a brief episode of status epilepticus results in chronic recurrent seizures, anxiety-like behavior, and destruction of hippocampal neurons. We used a chemical-genetic approach to selectively inhibit activation of TrkB. We demonstrate that inhibition of TrkB commencing after status epilepticus and continued for 2 weeks prevents recurrent seizures, ameliorates anxiety-like behavior, and limits loss of hippocampal neurons when tested weeks to months later. That transient inhibition commencing after status epilepticus can prevent these long-lasting devastating consequences establishes TrkB signaling as an attractive target for developing preventive treatments of epilepsy in humans.
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Transient inhibition of the BDNF receptor TrkB after seizure induction prevents the development of temporal lobe epilepsy.
“Other studies have shown that transient inhibition of the BDNF receptor TrkB after seizure induction prevents the development of temporal lobe epilepsy [186, 187].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [186]
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- Authors
- Liu, G., Gu, B., He, X.-P., Joshi, R. B., Wackerle, H. D., Rodriguiz, R. M., Wetsel, W. C., & McNamara, J. O.
- Affiliations
- Duke Medical Center (US)
- Duke University (US)
- Corresponding author
- McNamara, James O.
- Venue
- Neuron
- Publisher
- Elsevier BV
- Published
- 2013-07
- Volume
- 79
- Issue
- 1
- Pages
- 31-38
- ISSN
- 0896-6273 (ISSN-L)
- PMC
- PMC3744583
- OpenAlex
- W2078385314
- Cited by
- 210
- References
- 36
- Citations by year
- 2026: 8 · 2025: 3 · 2024: 12 · 2023: 7 · 2022: 6 · 2021: 16 · 2020: 18 · 2019: 29 · 2018: 15 · 2017: 26 · 2016: 26 · 2015: 15 · 2014: 24 · 2013: 5
- FWCI
- 16.53
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Licence
- Locations
- Neuron (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- DukeSpace (Duke University) (submittedVersion, cc-by-nc-nd)
- Funders
- National Institutes of Health
- National Institute of General Medical Sciences (T32GM008441)
- National Institute of Neurological Disorders and Stroke (NS56217, R01NS060728, R01NS056217, NS060728)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Health Sciences › Medicine › Pediatrics, Perinatology and Child Health › Pharmacological Effects and Toxicity Studies
- Keywords
- temporal lobe epilepsy, status epilepticus, BDNF receptor, epileptogenesis, hippocampal neuronal loss, anxiety-like behavior, recurrent seizures, epilepsy prevention, mouse model
- MeSH terms
- Amygdala, Animals, Behavior, Animal, Disease Models, Animal, Electroencephalography, Epilepsy, Temporal Lobe, Hippocampus, Kainic Acid, Motor Activity, Neurons, Status Epilepticus, Signal Transduction, Receptor, trkB, Mice
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