gms | German Medical Science

63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC)
Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS)

Deutsche Gesellschaft für Neurochirurgie (DGNC) e. V.

13. - 16. Juni 2012, Leipzig

Involvement of neuronal phosphotyrosine signal adaptor N-Shc in the kainic acid-induced epileptiform activity

Meeting Abstract

  • S. Baba - Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan; Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • S. Kakizawa - Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • K. Ohyama - Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • K. Yasuda - Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • T. Matuo - Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • N. Mori - Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan
  • Izumi Nagata - Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan

Deutsche Gesellschaft für Neurochirurgie. Japanische Gesellschaft für Neurochirurgie. 63. Jahrestagung der Deutschen Gesellschaft für Neurochirurgie (DGNC), Joint Meeting mit der Japanischen Gesellschaft für Neurochirurgie (JNS). Leipzig, 13.-16.06.2012. Düsseldorf: German Medical Science GMS Publishing House; 2012. DocP 039

DOI: 10.3205/12dgnc426, URN: urn:nbn:de:0183-12dgnc4267

Veröffentlicht: 4. Juni 2012

© 2012 Baba et al.
Dieser Artikel ist ein Open Access-Artikel und steht unter den Creative Commons Lizenzbedingungen (http://creativecommons.org/licenses/by-nc-nd/3.0/deed.de). Er darf vervielfältigt, verbreitet und öffentlich zugänglich gemacht werden, vorausgesetzt dass Autor und Quelle genannt werden.


Gliederung

Text

BDNF-TrkB signaling is implicated in experimental seizure and epilepsy. However, the downstream signaling mechanism of epileptogenesis from TrkB receptor activation is still controversial and whether it progresses through the PLCγ, Shc, or both is unclear. Recent studies have demonstrated that the so called PLCγ site, but not Shc site, plays an essential role in kindling development. However, it still remains unclear whether the Shc-mediated signaling pathway is exclusive to epileptiform activity and epileptogenesis. In the brain, signaling at the TrkB-Shc site, is transmitted through the neural-specific phosphotyrosine signal adaptor N-Shc. Therefore, the aim of this study is to examine whether N-Shc is involved in kainic acid (KA)-induced epileptiform activity. We show that pre-treating wild type mice with the TrkB inhibitor K252a significantly reduced the severity of KA-induced seizures, suggesting that TrkB-mediated signaling is crucial for the KA-induced seizure. Moreover, we show a significant reduction of both, the seizure scale and the frequency of epileptiform discharge, in the hippocampus of N-Shc deficient mice compared to the control mice. The KA-induced selective neuronal cell loss in the CA3 area of the hippocampus was also inhibited in the N-Shc deficient mice. These results suggest that N-Shc is essentially involved in the KA-induced epileptiform activity. We propose that the N-Shc-mediated signaling pathway would provide a potential target for the development of novel therapeutic drugs and/or approaches in the treatment of epilepsy.