Involvement of the neuronal phosphotyrosine signal adaptor N-Shc in kainic acid-induced epileptiform activity.
BDNF-TrkB signaling is implicated in experimental seizures and epilepsy. However, the downstream signaling involved in the epileptiform activity caused by TrkB receptor activation is still unknown. The aim of the present study was to determine whether TrkB-mediated N-Shc signal transduction was involved in kainic acid (KA)-induced epileptiform activity. We investigated KA-induced behavioral seizures, epileptiform activities and neuronal cell loss in hippocampus between N-Shc deficient and control mice. There was a significant reduction in seizure severity and the frequency of epileptiform discharges in N-Shc deficient mice, as compared with wild-type and C57BL/6 mice. KA-induced neuronal cell loss in the CA3 of hippocampus was also inhibited in N-Shc deficient mice. This study demonstrates that the activation of N-Shc signaling pathway contributes to an acute KA-induced epileptiform activity and neuronal cell loss in the hippocampus. We propose that the N-Shc-mediated signaling pathway could provide a potential target for the novel therapeutic approaches of epilepsy.
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.|Division of Neurology, The Hospital for Sick Children, Toronto, ON, Canada.
Shiro
S
Baba
Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Kazuko
K
Onga
Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Sho
S
Kakizawa
Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Kyoji
K
Ohyama
Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Kunihiko
K
Yasuda
Division of Neurology, The Hospital for Sick Children, Toronto, ON, Canada.
Hiroshi
H
Otsubo
Department of Pharmacology and Toxicology and the University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
Brian W
BW
Scott
Department of Pharmacology and Toxicology and the University of Toronto Epilepsy Research Program, Faculty of Medicine, University of Toronto, Toronto, ON, Canada.
W McIntyre
WM
Burnham
Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Takayuki
T
Matsuo
Department of Neurosurgery, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Izumi
I
Nagata
Department of Anatomy and Neurobiology, Nagasaki University Graduate School of Biomedical Sciences, Nagasaki, Japan.
Nozomu
N
Mori
D000818:Animals; D007608:Kainic Acid / Q000494:pharmacology*; D051379:Mice; D009474:Neurons / Q000378:metabolism*; D019000:Phosphotyrosine / Q000378:metabolism*; D012640:Seizures / Q000139:chemically induced / Q000378:metabolism*; D015398:Signal Transduction; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3 / Q000378:metabolism*
C485682:Shc3 protein, mouse; D000071427:Src Homology 2 Domain-Containing, Transforming Protein 3; D019000:Phosphotyrosine; D007608:Kainic Acid