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

2014 Fiscal Year Final Research Report

• Project/Area Number: 25861283
• Research Category: Grant-in-Aid for Young Scientists (B)
• Allocation Type: Multi-year Fund
• Research Field: Neurosurgery
• Research Institution: Nagasaki University
• Principal Investigator: BABA Shiro 長崎大学, 病院(医学系), 客員研究員 (30530430)
• Project Period (FY): 2013-04-01 – 2015-03-31
• Keywords: NShc / epilepsy / TrkB receptor / BDNF / kainic acid / hippocampus / neuronal cell death / seizure

Outline of Final Research Achievements

BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling mechanism in epileptiform activity and epileptogenesis caused by TrkB activation is still controversial. Signaling at the TrkB-Shc site is transmitted through the neural-specific phosphotyrosine signal adaptor NShc. Therefore, the aim of this study is to examine whether NShc-mediated signaling pathway is involved in kainic acid (KA)-induced epileptiform activity.
We show a significant reduction of both seizure severity and frequency of epileptiform discharges in NShc deficient mice as compared with control mice. KA-induced neuronal cell loss in the CA3 area of hippocampus was also inhibited in NShc deficient mice. These results suggest that NShc is involved in KA-induced epileptiform activity. We propose that the NShc-mediated signaling pathway could provide a potential target for the development of novel therapeutic drugs and/or approaches in the treatment of epilepsy.

Free Research Field

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