Differential vulnerability of hippocampus, basal ganglia, and prefrontal cortex to long-term NMDA excitotoxicity
Differential vulnerability of hippocampus, basal ganglia, and prefrontal cortex to long-term NMDA excitotoxicity
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DOI：
10.1006/exnr.1999.7293
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发表时间：
2000-02-01
影响因子：
5.3
通讯作者：
Mahy, N
中科院分区：
文献类型：
--
作者：
Bernal, F;Saura, J;Mahy, N
在人脑中，非动脉硬化性钙化与正常衰老和一些病理状态有关，但没有明确的意义。在所有情况下，钙化主要出现在基底神经节中，但也经常出现在海马和大脑皮层中。在大鼠中，α-氨基-（3-羟基-5-甲基-4-异恶唑-4-基）-丙酸诱导的苍白球损伤与钙沉积物的形成相关，类似于在人脑中观察到的钙沉积物。为了确定是否直接神经元激活可能会导致钙化，N-甲基-D-天冬氨酸（NMDA）在大鼠海马，苍白球，和外侧前额叶皮层显微注射。两个月后，神经元死亡与钙沉积有关，其特征在于分布和大小。一个独特的人口存款是目前在海马和前额叶皮层，而在苍白球两个主要群体可以区分。钙化总是与一个显着的小胶质细胞反应所示的外周苯二氮卓类受体放射自显影。反映星形胶质细胞反应的单胺氧化酶B放射自显影也显著增加。我们的研究结果提供的证据表明，急性NMDA神经元激活导致与神经胶质反应相关的钙化的时间，并表明，在人类大脑中的nonartherectin钙化可能从急性NMDA受体激活。代谢型mGluR 1受体的关键作用也被提出。(C)北京大学出版社.
In human brain, nonartherosclerotic calcification is associated with normal aging and several pathological conditions without any clear significance. In all situations, calcification appears predominantly in the basal ganglia, but is also frequent in the hippocampus and cerebral cortex, alpha-Amino-(3-hydroxi-5-methyl-4-isoxazol-4-il)-propionic acid-induced lesion of the globus pallidus is associated in rats with the formation of calcium deposits similar to those observed in the human brain. To determine whether direct neuronal activation may induce calcification, N-methyl-D-aspartate (NMDA) was microinjected in rat hippocampus, globus pallidus, and lateral prefrontal cortex. Two months later, neuronal death was associated with calcium deposits that were characterized in terms of distribution and size. A unique population of deposits was present in the hippocampus and prefrontal cortex, whereas in the globus pallidus two main groups could be differentiated. Calcification was always associated with a significant microglial reaction as shown by the peripheral benzodiazepine receptor autoradiography. Monoamine oxidase B autoradiography, reflecting the astroglial reaction, was also significantly increased. Our results provide evidence that acute NMDA neuronal activation leads with time to calcification associated with a glial reaction and indicate that nonartherosclerotic calcification in the human brain may develop from an acute NMDA receptor activation. A key role of the metabotropic mGluR1 receptor is also suggested. (C) 2000 Academic Press.