Okadaic acid induces epileptic seizures and hyperphosphorylation of the NR2B subunit of the NMDA receptor in rat hippocampus in vivo

被引:16
作者
Arias, C
Montiel, T
Peña, F
Ferrera, P
Tapia, R
机构
[1] Univ Nacl Autonoma Mexico, Dept Biol Celular & Fisiol, Inst Invest Biomed, Mexico City 04510, DF, Mexico
[2] Univ Nacl Autonoma Mexico, Dept Neurociencias, Inst Fisiol Celular, Mexico City 04510, DF, Mexico
关键词
protein phosphatases; okadaic acid; epilepsy; NMDA receptor phosphorylation; neurodegeneration; hippocampus;
D O I
10.1006/exnr.2002.7988
中图分类号
Q189 [神经科学];
学科分类号
071006 ;
摘要
Overactivation of N-methyl-D-aspartate (NAIDA) glutamate receptors is closely related to epilepsy and excitotoxicity, and the phosphorylation of these receptors may facilitate glutamate-mediated synaptic transmission. Here we show that in awake rats the microinjection into the hippocampus of okadaic acid, a potent inhibitor of protein phosphatases I and 2A, induces in about 20 min intense electroencephalographic and behavioral limbic-type seizures, which are suppressed by the systemic administration of the NMDA receptor antagonist (+)-5-methyl-10,11-dihydro-5H-dibenzo-[a,d]cyclohepten-5,10-imine hydrogen maleate and by the intrahippocampal administration of 1-(5-isoquinolinesulfonyl)-2-methylpiperazine, an inhibitor of protein kinases. Two hours after okadaic acid, when the EEG seizures were intense, an increased serine phosphorylation of some hippocampal proteins, including an enhancement of the serine phosphorylation of the NMDA receptor subunit NR2B, was detected by immunoblotting. Twenty-four hours after okadaic acid a marked destruction of hippocampal CA1 region was observed, which was not prevented by the receptor antagonists. These findings suggest that hyperphosphorylation of glutamate receptors in vivo may result in an increased sensitivity to the endogenous transmitter and therefore induce neuronal hyperexcitability and epilepsy. (C) 2002 Elsevier Science (USA).
引用
收藏
页码:284 / 291
页数:8
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