Effects of NMDA and its antagonists on ventral horn cholinergic neurons in organotypic roller tube spinal cord cultures.
Effects of NMDA and its antagonists on ventral horn cholinergic neurons in organotypic roller tube spinal cord cultures.
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NMDA 及其拮抗剂对器官型滚管脊髓培养物中腹角胆碱能神经元的影响。
DOI：
10.1007/bf01271292
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发表时间：
1997
期刊：
影响因子：
--
通讯作者：
Geula,C
中科院分区：
文献类型：
--
作者：
Delfs,JR;Saroff,DM;Nishida,Y;Friend,J;Geula,C
用胆碱乙酰转移酶（ChAT）、乙酰胆碱酯酶（AChE）活性测定和AChE组织化学方法，研究了兴奋性氨基酸（EAA）受体激动剂N-甲基-D-天冬氨酸（NMDA）及其拮抗剂对脊髓前角胆碱能神经元的神经毒性作用。NMDA暴露使ChAT和AChE活性分别降低83%和66%。NMDA处理的文化也表现出显着的损失AChE染色在背角和腹角和腹角AChE阳性神经元（VHANs）的数量显着，剂量依赖性减少。NMDA处理主要导致小VHAN（<300μm2）的损失。VHAN具有α运动神经元的典型大小和分布，保存相对较好。NMDA对OTC-SC的影响似乎与培养物的年龄无关。NMDA拮抗剂DL-AP 5可完全阻断NMDA诱导的ChAT活性的丧失，但仅减弱NMDA对AChE活性的影响。单独使用拮抗剂DL-AP 5、D-AP 5和MK-801引起VHAN的显著损失和/或收缩。这些作用似乎与NMDA介导的毒性不同。结果表明，NMDA及其拮抗剂对腹角胆碱能神经元有明显的毒性作用。然而，大的胆碱能α运动神经元似乎对这些毒性作用相对免疫。
Neurotoxic effects of excitatory amino acid (EAA) receptor agonist N-methyl-D-aspartic acid (NMDA) and its antagonists on ventral horn cholinergic neurons were studied in organotypic rollertube cultures of spinal cord (OTC-SCs) using biochemical assays of choline acetyltransferase (ChAT) and acetylcholinesterase (AChE) activity, and AChE histochemistry. NMDA exposure decreased ChAT and AChE activity by 83% and 66%, respectively. Cultures treated with NMDA also showed a marked loss of AChE staining in both dorsal and ventral horns and a significant, dose-dependent decrease in the number of ventral horn AChE-positive neurons (VHANs). NMDA treatment primarily resulted in the loss of small VHANs (<300μm2). VHANs with a size and distribution typical of α-motoneurons were relatively well preserved. The effects of NMDA on OTC-SCs appeared to be independent of the age of the cultures. The NMDA antagonist DL-AP5 completely prevented the NMDA-induced loss of ChAT activity, but only attenuated the effect of NMDA on AChE activity. The antagonists DL-AP5, D-AP5 and MK-801, used alone, caused significant loss and/or shrinkage of VHANs. These effects appeared to be distinct from the NMDA mediated toxicity. The results indicate that NMDA and its antagonists exert powerful toxic effects on ventral horn cholinergic neurons. The large cholinergic α-motoneurons, however, appear to be relatively immune to these toxic effects.