Previous studies of acrylamide (ACR) neuropathy in rat PNS [Toxicol. Appl. Pharmacol. (1998) 151:211-221] and in spinal cord, brainstem and cerebellum [NeuroToxicology (2002a) 23:397-414; NeuroToxicology (2002b) 23:415-429] have suggested that axon degeneration was not a primary effect and was, therefore, of unclear neurotoxicological significance. To conclude our studies of neurodegeneration in rat CNS during ACR neurotoxicity, a cupric silver stain method was used to define spatiotemporal characteristics of nerve cell body, dendrite, axon and terminal argyrophilia in forebrain regions and nuclei. Rats were exposed to ACR at a dose-rate of either 50 mg/kg per day (i.p.) or 21 mg/kg per day (p.o.) and at selected times brains were removed and processed for silver staining. Results show that intoxication at either ACR dose-rate produced a terminalopathy, i.e. nerve terminal degeneration and swelling were present in the absence of significant argyrophilic changes in neuronal cell bodies, dendrites or axons. Exposure to the higher ACR dose-rate caused early onset (day 5), widespread nerve terminal degeneration in most of the major forebrain areas, e.g. cerebral cortex, thalamus, hypothalamus and basal ganglia. At the lower dose-rate, nerve terminal degeneration in the forebrain developed early (day 7) but exhibited a relatively limited spatial distribution, i.e. anteroventral thalamic nucleus and the pars reticulata of the substantia nigra. Several hippocampal regions were affected at a later time point (day 28), i.e. CA1 field and subicular complex. At both dose-rates, argyrophilic changes in forebrain nerve terminals developed prior to the onset of significant gait abnormalities. Thus, in forebrain, ACR intoxication produced a pure terminalopathy that developed prior to the onset of significant neurological changes and progressed as a function of exposure. Neither dose-rate used in this study was associated with axon degeneration in any forebrain region. Our findings indicate that nerve terminals were selectively affected in forebrain areas and, therefore, might be primary sites of ACR action.

中文翻译：

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丙烯酰胺神经病。三，前脑神经细胞损伤的时空特征。

先前对大鼠PNS中丙烯酰胺（ACR）神经病的研究[毒理学杂志。应用 Pharmacol。（1998）151：211-221]和在脊髓，脑干和小脑中[NeuroToxicology（2002a）23：397-414; NeuroToxicology（2002b）23：415-429]提示轴突变性不是主要作用，因此尚不清楚神经毒理学的意义。为了结束我们对ACN神经毒性期间大鼠中枢神经系统神经变性的研究，使用铜银染色方法来定义前脑区域和细胞核中神经细胞体，树突，轴突和终末嗜银粒细胞的时空特征。将大鼠以每天50 mg / kg（ip）或每天21 mg / kg（po）的剂量率暴露于ACR，并在选定的时间取出大脑并进行银染处理。结果表明，在任一ACR剂量率下的中毒都会产生一种终末病，即在神经元细胞体，树突或轴突中不存在明显的嗜银性改变的情况下，会出现神经末梢变性和肿胀。暴露于较高的ACR剂量率会导致早期发作（第5天），在大多数主要前脑区域（例如大脑皮层，丘脑，下丘脑和基底神经节）中广泛的神经末梢变性。在较低的剂量率下，前脑的神经末梢退化发生得较早（第7天），但表现出相对有限的空间分布，即前腹丘脑核和黑质的网状体。在以后的某个时间点（第28天），几个海马区域受到了影响，即CA1视野和亚微带复合体。在两种剂量率下 在出现明显的步态异常之前，前脑神经末梢出现了嗜油性变化。因此，在前脑中，ACR中毒会产生纯的终末病，这种终末病会在重大的神经系统变化发生之前发展，并随着暴露而发展。这项研究中使用的两种剂量率均与任何前脑区域的轴突变性均无关。我们的发现表明，神经末梢在前脑区域受到选择性影响，因此可能是ACR作用的主要部位。这项研究中使用的两种剂量率均与任何前脑区域的轴突变性均无关。我们的发现表明，神经末梢在前脑区域受到选择性影响，因此可能是ACR作用的主要部位。这项研究中使用的两种剂量率均与任何前脑区域的轴突变性均无关。我们的发现表明，神经末梢在前脑区域受到选择性影响，因此可能是ACR作用的主要部位。