Zhang X, Zuo D M, Davis B A, Boulton A A, Yu P H
Neuropsychiatry Research Unit, University of Saskatchewan, Saskatoon, Canada.
J Neurosci Res. 1996 Feb 15;43(4):482-9. doi: 10.1002/(SICI)1097-4547(19960215)43:4<482::AID-JNR9>3.0.CO;2-B.
DSP-4 [N-(2-chloroethyl)-N-ethyl-2-bromobenzylamine] is a potent neurotoxin highly selective to the locus coeruleus noradrenaline (NA) system. Previous biochemical studies have shown that the monoamine oxidase-B (MAO-B) inhibitors, R(-)-deprenyl and (+/-)2-HxMP [N-(2-hexyl)-N-methylpropargylamine], are able to prevent DSP-4 induced NA depletion in the mouse hippocampus. It is not quite certain, however, whether this actually represents neuroprotection of NA axons or a metabolic effect due to inhibition of MAO activity. Employing dopamine-beta-hydroxylase immunohistochemical and image analysis methods, we have shown that 92% and 84% of NA nerve fibers in the rat hippocampus are spared from DSP-4 neurotoxicity by a single pretreatment dose of either R(-)-deprenyl or (+/-)2-HxMP respectively. Similar neuroprotective effects of R(-)-deprenyl and (+/-)2-HxMP were also observed in the cerebral cortex, thalamus, amygdaloid complex and cerebellum. This is the first morphological evidence demonstrating that R(-)-deprenyl and (+/-)2-HxMP can indeed protect noradrenergic axons of locus coeruleus origin against DSP-4 neurotoxicity.
DSP-4 [N-(2-氯乙基)-N-乙基-2-溴苄胺] 是一种对蓝斑去甲肾上腺素（NA）系统具有高度选择性的强效神经毒素。先前的生化研究表明，单胺氧化酶-B（MAO-B）抑制剂R(-)-司来吉兰和(+/-)2-HxMP [N-(2-己基)-N-甲基炔丙胺] 能够预防DSP-4诱导的小鼠海马体中NA耗竭。然而，这实际上是否代表对NA轴突的神经保护作用或由于MAO活性抑制导致的代谢效应尚不完全确定。采用多巴胺-β-羟化酶免疫组织化学和图像分析方法，我们发现，大鼠海马体中分别用单剂量的R(-)-司来吉兰或(+/-)2-HxMP预处理后，92%和84%的NA神经纤维免受DSP-4神经毒性影响。在大脑皮层、丘脑、杏仁复合体和小脑中也观察到了R(-)-司来吉兰和(+/-)2-HxMP类似的神经保护作用。这是首个形态学证据，证明R(-)-司来吉兰和(+/-)2-HxMP确实能够保护蓝斑起源的去甲肾上腺素能轴突免受DSP-4神经毒性影响。
