Comprehensive research of MMP gene in an animal model of epileptic seizure

MMP基因在癫痫发作动物模型中的综合研究

• 批准号: 21790068
• 负责人: MIZOGUCHI Hiroyuki
• 金额: $ 2.75万
• 依托单位: Nagoya University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Young Scientists (B)
• 财政年份: 2009
• 资助国家: 日本
• 起止时间: 2009 至 2010
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-21790068/
• 关键词: MMP; BDNF; てんかん; キンドリング; 海馬; 苔状線維

In the present study, we investigated the role of matrix metalloproteinase (MMP)-9 in the development of pentylenetetrazole (PTZ)-induced kindled seizure in mice. Repeated treatment with PTZ (40 mg/kg) produced kindled seizure, which was accompanied by enhanced MMP-9 activity and expression in the hippocampus. No change in MMP-9 activity was observed in the hippocampi of mice with generalized tonic seizure following single administration of PTZ (60 mg/kg). MMP-9 colocalized with the neuronal marker NeuN and the glial marker GFAP in the dentate gyrus of the kindled mouse hippocampus. Coadministration of diazepam or MK-801 with PTZ inhibited the development of kindling and the increased MMP-9 levels in the hippocampus. Marked suppression of kindled seizure progression in response to repeated PTZ treatment was observed in MMP-9^<(-/-)> mice compared with wild-type mice, an observation that was accompanied by decreased hippocampal levels of mature brain-derived neurotrophic factor (BDNF) despite similar BDNF mRNA levels. These findings suggest that MMP-9 is involved in progression of behavioral phenotypes in kindled mice owing to conversion of pro-BDNF to mature BDNF in the hippocampus.

在本研究中，我们研究了基质金属蛋白酶(MMP)-9在戊四唑（PTZ）诱发小鼠点燃性癫痫发作中的作用。反复给予PTZ （40 mg/kg）可引起点燃性癫痫发作，并伴有海马中MMP-9活性和表达增强。单次给药（60 mg/kg）后，全身性强直性癫痫小鼠海马组织中MMP-9活性未见变化。MMP-9在点燃小鼠海马齿状回中与神经元标记物NeuN和胶质标记物GFAP共定位。地西泮或MK-801与PTZ共给药可抑制点燃的发生和海马中MMP-9水平的升高。与野生型小鼠相比，MMP-9^<(-/-)>小鼠对重复PTZ治疗的点燃性癫痫进展有明显抑制，这一观察结果伴随着海马成熟脑源性神经营养因子（BDNF）水平的降低，尽管BDNF mRNA水平相似。这些发现表明，MMP-9参与了点燃小鼠海马中促BDNF向成熟BDNF转化的行为表型的进展。

项目成果

ラットを用いた意思決定の行動学的解析:放射状迷路を用いた小動物用ギャンブルテスト

使用大鼠进行决策的行为分析：使用径向迷宫对小动物进行赌博测试

• 发表时间: 2010
• 作者: 溝口博之;他
• 通讯作者: 他

Yamada K Alterations of emotional and cognitive behaviors in matrix metalloproteinase-2 and -9-deficient mice.

Yamada K 基质金属蛋白酶-2 和-9 缺陷小鼠情绪和认知行为的改变。

• 发表时间: 2010
• 期刊: The Open Behav Sci J. 4
• 作者: Mizoguchi H;Ibi D;Takuma K;Toth E;Sato J;Itohara S;Nabeshima T
• 通讯作者: Nabeshima T

意思決定の行動学的解析:放射状迷路を用いた小動物用ギャンブルテスト

决策行为分析：使用径向迷宫对小动物进行赌博测试

• 发表时间: 2010
• 作者: 溝口博之;他
• 通讯作者: 他

Involvement of matrix metalloproteinase-9 in the development of pentyl eneterazole-induced kindled seizure in mice.

基质金属蛋白酶 9 参与戊基四唑诱导的小鼠点燃癫痫发作的发生。

• 发表时间: 2009
• 作者: Hiroyuki Mizoguchi;et al.
• 通讯作者: et al.

Nicotine ameliorates impairment of working memory in methamphetamine-treated rats.

尼古丁可改善甲基苯丙胺治疗大鼠的工作记忆损伤。

• 发表时间: 2011
• 期刊: Behav Brain Res. 220
• 作者: Mizoguchi H;Ibi D;Takase F;Nagai T;Kamei H;Toth E;Sato J;Takuma K;Yamada K.
• 通讯作者: Yamada K.