DIFFERENTIAL SPARING OF SOMATOSTATIN-NEUROPEPTIDE-Y AND CHOLINERGIC NEURONS FOLLOWING STRIATAL EXCITOTOXIN LESIONS
DIFFERENTIAL SPARING OF SOMATOSTATIN-NEUROPEPTIDE-Y AND CHOLINERGIC NEURONS FOLLOWING STRIATAL EXCITOTOXIN LESIONS
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DOI：
10.1002/syn.890030106
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发表时间：
1989-01-01
期刊：
影响因子：
2.3
通讯作者：
MARTIN, JB
中科院分区：
文献类型：
--
作者：
BEAL, MF;KOWALL, NW;MARTIN, JB
我们以前发现，喹啉酸纹状体兴奋性毒素病变导致生长抑素和神经肽Y神经元的相对保留。在本研究中，我们检查了兴奋性毒素作用于谷氨酸受体的三种亚型的剂量反应效应：N-甲基-D-天冬氨酸（AA 1），使君子酸（AA 2）和红藻氨酸（AA 3）。将生长抑素样免疫反应性（SLI）和神经肽A Y样免疫反应性（NPYLI）的浓度与P物质样免疫反应性（SPLI）和GABA的浓度进行比较。红藻氨酸（AA 3）、使君子酸（AA 2）和AMPA（AA 2）导致检查的所有四种神经化学标志物的剂量依赖性降低，而N-甲基-D，L-天冬氨酸（AA 1）和喹啉酸（AA 1）导致SLI和NPYLI相对减少。在导致GABA和SPLI均降低50%的各兴奋性毒素剂量下，仅N-甲基-D，L-天冬氨酸和喹啉酸对SLI和NPYLI的浓度无显著影响。通过使用NADPH-黄递酶神经元的组织化学染色结合尼氏染色或脑啡肽的免疫组织化学染色，在组织学上证实了生长抑素-神经肽Y神经元的相对保留。用N-甲基-D-天冬氨酸激动剂的损伤导致优先保留NADPH-黄递酶神经元，而这些神经元比其他神经元更容易受到红藻氨酸或AMPA的影响。胆碱乙酰转移酶神经元相对幸免，与其他神经元相比，代理人在所有三个谷氨酸受体亚型。MK-801可阻断N-甲基-D，L-天冬氨酸病变，而对使君子酸或红藻氨酸病变无影响。使用N-甲基-D-天冬氨酸（AA 1）激动剂进行纹状体兴奋性毒素损伤后，生长激素抑制素-神经肽Y神经元的相对保留可能反映了这些神经元上AA 1受体的缺乏。由于这些神经元在亨廷顿氏病中也不存在，因此作用于N-甲基-D-天冬氨酸（AA 1）位点的兴奋性毒素提供了这种疾病的改进的神经化学模型。
We previously found that quinolinic acid striatal excitotoxin lesions result in a relative sparing of somatostatin and neuropeptide Y neurons. In the present study we examined dose‐response effects of excitotoxins acting at the three subtypes of glutamate receptors: N‐methyl‐D‐aspartate (AA1), quisqualate (AA2), and kainic acid (AA3). Concentrations of both somatostatin‐like immunoreactivity (SLI) and neuropeptide a Y‐like immunoreactivity (NPYLI) were compared with those of substance P‐like immunoreactivity (SPLI) and GABA. Kainic acid (AA3), quisqualic acid (AA2), and AMPA (AA2) resulted in dose‐dependent reductions in all four neurochemical markers examined, while N‐methyl‐D,L‐aspartate (AA1) and quinolinic acid (AA1) resulted in relative sparing of SLI and NPYLI. At doses of each excitotoxin which resulted in comparable 50% reductions in both GABA and SPLI only N‐methyl‐D,L‐aspartate and quinolinic acid had no significant effect on concentrations of SLI and NPYLI. The relative sparing of somatostatin‐neuropeptide Y neurons was confirmed histologically by using histochemical staining for NADPH‐diaphorase neurons combined with either Nissl stains, or immunohistochemical staining for enkephalin. Lessions with N‐methyl‐D‐aspartate agonists resulted in preferential sparing of NADPH‐diaphorase neurons while these neurons were more vulnerable than other neurons to kainic acid or AMPA. Choline acetyltransferase neurons were relatively spared, as compared with other neurons, by agents acting at all three glutamate receptor subtypes. N‐methyl‐D,L‐aspartate lesions were blocked with MK‐801, while there was no effect on quisqualic acid or kainic acid lesions. The relative sparing of somatostatin‐neuropeptide Y neurons following striatal excitotoxin lesions with N‐methyl‐D‐aspartate (AA1) agonists probably reflects a paucity of AA1 receptors on these neurons. Since these neurons are also spared in Huntington's disease, excitotoxins acting at the N‐methyl‐D‐aspartate (AA1) site provide an improved neurochemical model of this illness.