BDNF-TrkB signaling pathway mediates the induction of epileptiform activity induced by a convulsant drug cyclothiazide
Open accessAbstract
Brain-derived neurotrophic factor (BDNF) and its receptor TrkB play an important function in neuronal development and synaptic plasticity. Recently we have established that cyclothiazide (CTZ) is a novel convulsant drug inducing robust epileptiform activity in hippocampal neurons both in vitro and in vivo. However, the molecular mechanisms underlying such convulsant action of CTZ are unknown. Here, we investigated potential roles of BDNF-TrkB signaling pathway in the CTZ-induction of epileptiform activity. In anaesthetized rats, CTZ dose-dependently induced epileptiform activity characterized by progressing of multiple peaks of population spikes, spontaneous spiking events, and synchronized epileptiform bursts. Pre-injection of a receptor tyrosine kinase inhibitor K252a or a specific antibody for TrkB receptors before intracerebroventricular injection of CTZ significantly suppressed the epileptiform activity induced by CTZ. Similarly, in cultured hippocampal pyramidal neurons, pre-treatment with CTZ together with K252a or TrkB-receptor antibody also inhibited the CTZ-induction of epileptiform activity. Furthermore, we demonstrated that acute application of K252a in hippocampal cultures inhibited epileptiform bursts and action potential firing. We conclude that activation of BDNF-TrkB signaling pathway is fundamentally important during the CTZ-induction of epileptiform activity both in vitro and in vivo.
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Seizures are associated with increased expression of several neurotrophic-related genes, including transcription factors, neuropeptides, and growth factors.
“Seizures have been associated with an increased expression of several neurotrophic-related genes, including transcription factors [176], neuropeptides [177], and growth factors [178].”
From Brain-Derived Neurotrophic Factor in Brain Disorders: Focus on Neuroinflammation (2019) · cites this paper as [178]
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- Authors
- Wang, Y., Qi, J.-S., Kong, S., Sun, Y., Fan, J., Jiang, M., & Chen, G.
- Affiliations
- Chongqing Technology and Business University (CN)
- Pennsylvania State University (US)
- Fudan University (CN)
- Corresponding author
- Wang, Yun
- Chen, Gong
- Venue
- Neuropharmacology
- Publisher
- Elsevier BV
- Published
- 2009-07
- Volume
- 57
- Issue
- 1
- Pages
- 49-59
- ISSN
- 0028-3908 (ISSN-L)
- PMC
- PMC2733837
- OpenAlex
- W1979787584
- Cited by
- 39
- References
- 42
- Citations by year
- 2026: 2 · 2025: 2 · 2024: 1 · 2023: 4 · 2022: 3 · 2018: 3 · 2017: 2 · 2016: 1 · 2015: 5 · 2014: 4 · 2013: 5 · 2012: 3
- FWCI
- 1.44
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Neuropharmacology (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Natural Science Foundation of China
- National Institute of Neurological Disorders and Stroke (R21NS054858, NS054858)
- Topics
- Health Sciences › Medicine › Psychiatry and Mental health › Epilepsy research and treatment
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Neuroscience and Neuropharmacology Research
- Life Sciences › Neuroscience › Cellular and Molecular Neuroscience › Nerve injury and regeneration
- Keywords
- BDNF/TrkB signaling, cyclothiazide, epileptiform activity, convulsant drugs, K252a, TrkB receptor, hippocampal neurons, receptor tyrosine kinase, seizure induction, population spike, action potential firing
- MeSH terms
- Action Potentials, Analysis of Variance, Animals, Antibodies, Antihypertensive Agents, Benzothiadiazines, Carbazoles, Disease Models, Animal, Dose-Response Relationship, Drug, Enzyme Inhibitors, Epilepsy, Hippocampus, Male, Neurons, Time Factors, Signal Transduction, Rats, Sprague-Dawley, Brain-Derived Neurotrophic Factor, Receptor, trkB, Indole Alkaloids, Rats, In Vitro Techniques
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