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

Publication ,  Journal Article
Liu, G; Gu, B; He, X-P; Joshi, RB; Wackerle, HD; Rodriguiz, RM; Wetsel, WC; McNamara, JO
Published in: Neuron
July 10, 2013

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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Published In

Neuron

DOI

EISSN

1097-4199

Publication Date

July 10, 2013

Volume

79

Issue

1

Start / End Page

31 / 38

Location

United States

Related Subject Headings

  • Status Epilepticus
  • Signal Transduction
  • Receptor, trkB
  • Neurons
  • Neurology & Neurosurgery
  • Motor Activity
  • Mice
  • Kainic Acid
  • Hippocampus
  • Epilepsy, Temporal Lobe
 

Citation

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Liu, G., Gu, B., He, X.-P., Joshi, R. B., Wackerle, H. D., Rodriguiz, R. M., … McNamara, J. O. (2013). Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy. Neuron, 79(1), 31–38. https://doi.org/10.1016/j.neuron.2013.04.027
Liu, Gumei, Bin Gu, Xiao-Ping He, Rasesh B. Joshi, Harold D. Wackerle, Ramona Marie Rodriguiz, William C. Wetsel, and James O. McNamara. “Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy.Neuron 79, no. 1 (July 10, 2013): 31–38. https://doi.org/10.1016/j.neuron.2013.04.027.
Liu G, Gu B, He X-P, Joshi RB, Wackerle HD, Rodriguiz RM, et al. Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy. Neuron. 2013 Jul 10;79(1):31–8.
Liu, Gumei, et al. “Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy.Neuron, vol. 79, no. 1, July 2013, pp. 31–38. Pubmed, doi:10.1016/j.neuron.2013.04.027.
Liu G, Gu B, He X-P, Joshi RB, Wackerle HD, Rodriguiz RM, Wetsel WC, McNamara JO. Transient inhibition of TrkB kinase after status epilepticus prevents development of temporal lobe epilepsy. Neuron. 2013 Jul 10;79(1):31–38.
Journal cover image

Published In

Neuron

DOI

EISSN

1097-4199

Publication Date

July 10, 2013

Volume

79

Issue

1

Start / End Page

31 / 38

Location

United States

Related Subject Headings

  • Status Epilepticus
  • Signal Transduction
  • Receptor, trkB
  • Neurons
  • Neurology & Neurosurgery
  • Motor Activity
  • Mice
  • Kainic Acid
  • Hippocampus
  • Epilepsy, Temporal Lobe