Neuron
Volume 79, Issue 1, 10 July 2013, Pages 31-38
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Transient Inhibition of TrkB Kinase after Status Epilepticus Prevents Development of Temporal Lobe Epilepsy

https://doi.org/10.1016/j.neuron.2013.04.027Get rights and content
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Highlights

  • Prevention of temporal lobe epilepsy

  • Prevention of behavioral comorbidity of epilepsy

  • TrkB signaling is an attractive target for prevention of epilepsy

  • Time course of effective treatment enhances feasibility for translation

Summary

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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Present Address: U.S. Food and Drug Administration, Silver Spring, MD 20993, USA

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These authors contributed equally to this work