Selective cholinergic neurotoxin: AF64A's effects in rat striatum.
Selective cholinergic neurotoxin: AF64A's effects in rat striatum.
复制标题
选择性胆碱能神经毒素：AF64A 对大鼠纹状体的影响。
DOI：
10.1016/0006-8993(84)91451-3
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发表时间：
1984
期刊：
影响因子：
2.9
通讯作者：
Coyle,JT
中科院分区：
文献类型：
--
作者：
Sandberg,K;Hanin,I;Fisher,A;Coyle,JT
用脑立体定向法将乙基胆碱的氮丙啶离子（AF 64 A）注入大鼠纹状体，观察其选择性神经毒性作用。在剂量-反应研究（2-26 nmol）中，8 nmol导致纹状体胆碱乙酰转移酶（CAT）活性降低46%，7天时对谷氨酸脱羧酶（GAD）和酪氨酸羟化酶（TH）活性的影响极小。最大CAT减少78-82%发生在16-26 nmol的剂量，这也导致GAD和TH活性的剂量相关性降低，抑制CAT的进行性递减。8 nmol的时程研究表明，CAT活性在12小时内迅速降低20%，在接下来的一周内又逐渐下降20%; TH和GAD活性没有显着降低。CAT活性的选择性抑制持续至少3个月。尼氏染色切片的组织学检查显示，注射部位有一个非特异性损伤区域，其边界突然被明显正常的纹状体神经元包围;然而，乙酰胆碱酯酶的神经元胞体染色强度并未降低。这些初步研究结果强烈表明，AF 64 A对纹状体胆碱能神经元具有选择性神经毒性作用，而相对保留纹状体GABA能内源性神经元或多巴胺能传入。
The selective neurotoxic effects of the aziridinium ion of ethylcholine (AF64A) have been examined after stereotaxic injection into the rat striatum. In a dose-response study (2–26 nmol), 8 nmol caused a 46% decrease in striatal choline acetyltransferase (CAT) activity with minimal effects on the activities of glutamate decar☐ylase (GAD) and tyrosine hydroxylase (TH) at 7 days. Maximal CAT reductions of 78–82% occurred with doses of 16–26 nmol which also caused dose-related decreases in GAD and TH activities that paralleled the progressive decrements in CAT. A time course study with 8 nmol indicated a rapid 20% reduction of CAT activity by 12 h and an additional gradual fall of 20% over the next week; TH and GAD activities were not significantly reduced. The selective inhibition of CAT activity persisted for at least 3 months. Histological examination of Nissl stained sections revealed an area of non-specific damage at the injection site with an abrupt border surrounded by apparently normal striatal neuropil; however, neuronal perikarya staining intensely for acetylcholinesterase were not reduced. These preliminary findings strongly suggest that AF64A has selective neurotoxic effects against striatal cholinergic neurons while relatively sparing striatal GABAergic intrinsic neurons or dopaminergic afferents.