Involvement of p38alpha in kainate-induced seizure and neuronal cell damage.
We investigated how p38alpha mitogen-activated protein kinase (p38) is related to kainate-induced epilepsy and neuronal damages, by using the mice with a single copy disruption of the p38 alpha gene (p38alpha(+/-)). Mortality rate and seizure score of p38alpha(+/-) mice administered with kainate were significantly reduced compared with the case of wild-type (WT) mice. This was clearly supported by the electroencephalography data in which kainate-induced seizure duration and frequency in the brain of p38alpha(+/-) mice were significantly suppressed compared to those of WT mice. As a consequence of seizure, kainate induced delayed neuronal damages in parallel with astrocytic growth in the hippocampus and ectopic innervation of the mossy fibers into the stratum oriens in the CA3 region of hippocampus in WT mice, whose changes were moderate in p38alpha(+/-) mice. Likewise, kainate-induced phosphorylation of calcium/calmodulin-dependent kinase II in the hippocampus of p38alpha (+/-) mice was significantly decreased compared to that of WT mice. These results suggest that p38alpha signaling pathway plays an important role in epileptic seizure and excitotoxicity.
Namiki
Kana
K
Department of Biochemistry and Molecular Pharmacology, Graduate School of Medicine, Chiba University, 1-8-1 Inohana, Chuo-ku, Chiba 260-8670, Japan.
Nakamura
Akira
A
Furuya
Mitsuko
M
Mizuhashi
Satomi
S
Matsuo
Yuji
Y
Tokuhara
Naoki
N
Sudo
Tatsuhiko
T
Hama
Hiroshi
H
Kuwaki
Tomoyuki
T
Yano
Shingo
S
Kimura
Sadao
S
Kasuya
Yoshitoshi
Y
D000818:Animals; D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism; D004569:Electroencephalography; D005260:Female; D007608:Kainic Acid / Q000494:pharmacology*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D048308:Mitogen-Activated Protein Kinase 14 / Q000378:metabolism*; D019599:Mossy Fibers, Hippocampal / Q000254:growth & development; D009474:Neurons / Q000187:drug effects* / Q000473:pathology*; D010766:Phosphorylation; D012640:Seizures / Q000139:chemically induced* / Q000201:enzymology* / Q000473:pathology; D013997:Time Factors
D054732:Calcium-Calmodulin-Dependent Protein Kinase Type 2; D017871:Calcium-Calmodulin-Dependent Protein Kinases; D048308:Mitogen-Activated Protein Kinase 14; D007608:Kainic Acid