Differential NMDA receptor-dependent calcium loading and mitochondrial dysfunction in CA1 vs. CA3 hippocampal neurons.
Differential NMDA receptor-dependent calcium loading and mitochondrial dysfunction in CA1 vs. CA3 hippocampal neurons.
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DOI：
10.1016/j.nbd.2009.10.020
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发表时间：
2010-02
影响因子：
6.1
通讯作者：
Andrews SB
中科院分区：
文献类型：
--
作者：
Stanika RI;Winters CA;Pivovarova NB;Andrews SB
海马CA1区锥体神经元选择性地易受缺血损伤，而邻近的CA3区神经元相对抵抗缺血损伤。虽然谷氨酸受体介导的线粒体Ca2+超载和功能障碍是缺血诱导的神经元死亡的主要组成部分，选择性神经元脆弱性和线粒体功能障碍之间没有直接的关系已被证明在完整的脑制剂。在这里，我们表明，在器官型切片培养NMDA诱导更大的Ca 2+升高在脆弱的CA 1神经元比抵抗CA 3。因此，CA 1线粒体表现出更强的钙积累，更广泛的肿胀和损伤，更强的去极化，其膜电位，并在ROS的产生显着增加。NMDA诱导的Ca2+和ROS升高在无Ca2+培养基中或通过NMDAR拮抗剂被废除，但不通过锌螯合。我们的结论是，钙超载依赖性线粒体功能障碍是一个决定因素，在选择性的脆弱性CA1神经元。
Hippocampal CA1 pyramidal neurons are selectively vulnerable to ischemia, while adjacent CA3 neurons are relatively resistant. Although glutamate receptor-mediated mitochondrial Ca2+ overload and dysfunction is a major component of ischemia-induced neuronal death, no direct relationship between selective neuronal vulnerability and mitochondrial dysfunction has been demonstrated in intact brain preparations. Here, we show that in organotypic slice cultures NMDA induces much larger Ca2+ elevations in vulnerable CA1 neurons than in resistant CA3. Consequently, CA1 mitochondria exhibit stronger calcium accumulation, more extensive swelling and damage, stronger depolarization of their membrane potential, and a significant increase in ROS generation. NMDA-induced Ca2+ and ROS elevations were abolished in Ca2+-free medium or by NMDAR antagonists, but not by zinc chelation. We conclude that Ca2+-overload-dependent mitochondrial dysfunction is a determining factor in the selective vulnerability of CA1 neurons.
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DOI：
10.1074/jbc.m901203200
发表时间：
2009-05-22
期刊：
The Journal of biological chemistry
影响因子：
--
作者：
Dixon RM;Mellor JR;Hanley JG
通讯作者：
Hanley JG
影响因子：
3.3
作者：
Klapstein, GJ;Vietla, S;Mody, I
通讯作者：
Mody, I
影响因子：
5.5
作者：
Duan, Yuntao;Gross, Robert A.;Sheu, Shey-Shing
通讯作者：
Sheu, Shey-Shing
影响因子：
5.3
作者：
Calderone, A;Jover, T;Zukin, RS
通讯作者：
Zukin, RS
影响因子：
16.2
作者：
Bossy-Wetzel, E;Talantova, MV;Lipton, SA
通讯作者：
Lipton, SA