Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy.

Abstract

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.

• Authors: Gumei Liu, Bin Gu, Xiao-Ping He, Rasesh B Joshi, Harold D Wackerle, Ramona Marie Rodriguiz, William C Wetsel, James O McNamara
• Journal: Neuron (Neuron) Vol. 79 Issue 1 Pg. 31-8 (Jul 10 2013) ISSN: 1097-4199 [Electronic] United States
• PMID: 23790754 (Publication Type: Journal Article, Research Support, N.I.H., Intramural)
• Copyright: Copyright © 2013 Elsevier Inc. All rights reserved.

Chemical References

• Receptor, trkB
• Kainic Acid

Topics

• Amygdala (metabolism)
• Animals
• Behavior, Animal (physiology)
• Disease Models, Animal
• Electroencephalography
• Epilepsy, Temporal Lobe (etiology, genetics, prevention & control)
• Hippocampus (metabolism)
• Kainic Acid
• Mice
• Motor Activity (physiology)
• Neurons (metabolism)
• Receptor, trkB (genetics, metabolism)
• Signal Transduction (genetics)
• Status Epilepticus (chemically induced, complications, genetics)