Ablation of p27 enhance kainate-induced seizure and hippocampal degeneration.
p27 is a cyclin-dependent kinase inhibitor which arrests cell cycle at G1-S phase. Using RNA interference method, we previously showed that reduction of endogenous p27 expression induces cell death through cell cycle progression in cultured cortical neurons. In this study, we investigated responses to kainate treatment using p27 knockout mice. Injection of kainic acid induced p27 downregulation and retinoblastoma protein phosphorylation in wild-type mouse hippocampus. No change was observed in hippocampal cell viability in untreated adult p27 heterozygous and homozygous mice compared with wild type (+/+). p27 homozygous mice, however, displayed enhanced seizure and hippocampal degeneration after kainic acid treatment. This study first suggests that ablation of p27 enhance kainate-induced seizure and hippocampal cell death in vivo.
Ueyama
Chihiro
C
Laboratory of Chemical Pharmacology, Graduate School of Pharmaceutical Sciences, The University of Tokyo, Hongo, Bunkyo-ku, Tokyo, Japan.
Akashiba
Hiroki
H
Nakayama
Keiko
K
Nakayama
Keiichi I
KI
Nishiyama
Nobuyoshi
N
Matsuki
Norio
N
D000818:Animals; D015153:Blotting, Western; D002453:Cell Cycle / Q000187:drug effects; D050760:Cyclin-Dependent Kinase Inhibitor p27 / Q000235:genetics / Q000502:physiology*; D004247:DNA / Q000235:genetics; D018690:Excitatory Amino Acid Agonists / Q000633:toxicity*; D006624:Hippocampus / Q000473:pathology*; D007150:Immunohistochemistry; D007608:Kainic Acid / Q000037:antagonists & inhibitors* / Q000633:toxicity; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009410:Nerve Degeneration / Q000139:chemically induced* / Q000473:pathology*; D034622:RNA Interference; D020133:Reverse Transcriptase Polymerase Chain Reaction; D012640:Seizures / Q000139:chemically induced* / Q000235:genetics / Q000503:physiopathology*
D018690:Excitatory Amino Acid Agonists; D050760:Cyclin-Dependent Kinase Inhibitor p27; D004247:DNA; D007608:Kainic Acid