Veronesi B, Jones K, Gupta S, Pringle J, Mezei C
U.S. Environmental Protection Agency, Health Effects Research Laboratory, RTP, North Carolina 27711.
Neurotoxicology. 1991 Summer;12(2):265-76.
Triethyltin (TET) is a neurotoxicant that produces severe but transient cerebral edema, characterized ultrastructurally by vacuolation of the intraperiod line of central nervous system (CNS) myelin. TET has been reported to depress levels of myelin basic protein (MBP), a protein thought to play a critical role in myelin compaction. In the present study, the genomic expression (i.e., mRNA) of MBP was monitored throughout the pathogenesis of TET-induced myelin edema and recovery in Sprague-Dawley rats given a single injection of a neuropathic (8.0 mg/kg) or non-neuropathic (0.8 mg/kg) dose of TET-bromide. Levels of MBP-mRNA from the anterior and posterior brain were collected 1 hr, 3 hr, 2d, and 7d, postexposure. The optic nerve and caudal brainstem, representing anterior and posterior brain sites, respectively, were examined at the same time-points for ultrastructural evidence of edema and recovery. Our data indicate that neuropathic doses (8.0 mg/kg) of TET significantly stimulated MBP transcript throughout the brain at all exposure time-points. The magnitude and time-course of this stimulation differed in the anterior and posterior brain, with the latter region showing higher levels of MBP-mRNA. In the posterior brain, the highest levels of mRNA correlated with the appearance of edema in the caudal brainstem. In the anterior brain, MBP-mRNA levels were only marginally increased over controls. Ultrastructural evidence of myelin edema was confined to the brainstem in rats treated with neuropathic dose of TET. Intralamellar vacuolation appeared at 3 hr and 2d postexposure and could be correlated with peak levels of MBP transcript, whereas, recompacted myelin, which appeared by 7d postexposure, was associated with declining levels of the mRNA. Ultrastructural changes in the oligodendroglia were suggestive of metabolic stimulation and correlated with high MBP-mRNA levels. In summary, these data indicate that an initial genomic event in TET-induced myelin edema is stimulation of MBP transcript.
三乙基锡（TET）是一种神经毒物，可导致严重但短暂的脑水肿，其超微结构特征为中枢神经系统（CNS）髓鞘内周期线出现空泡化。据报道，TET会降低髓鞘碱性蛋白（MBP）的水平，MBP是一种被认为在髓鞘紧密化过程中起关键作用的蛋白质。在本研究中，对给予单次注射神经毒性（8.0 mg/kg）或非神经毒性（0.8 mg/kg）剂量的溴化TET的Sprague-Dawley大鼠，在TET诱导的髓鞘水肿发病及恢复的整个过程中监测MBP的基因表达（即mRNA）。在暴露后1小时、3小时、2天和7天收集前脑和后脑的MBP-mRNA水平。分别在前脑和后脑部位的视神经和尾侧脑干，在相同时间点检查水肿和恢复的超微结构证据。我们的数据表明，神经毒性剂量（8.0 mg/kg）的TET在所有暴露时间点均显著刺激全脑的MBP转录本。这种刺激的程度和时间进程在前脑和后脑有所不同，后脑区域的MBP-mRNA水平较高。在后脑，最高的mRNA水平与尾侧脑干水肿的出现相关。在前脑，MBP-mRNA水平仅比对照组略有增加。用神经毒性剂量的TET处理的大鼠，髓鞘水肿的超微结构证据仅限于脑干。板层内空泡化在暴露后3小时和2天出现，且与MBP转录本的峰值水平相关，而暴露后7天出现的重新紧密化的髓鞘与mRNA水平下降相关。少突胶质细胞的超微结构变化提示代谢受到刺激，且与高MBP-mRNA水平相关。总之，这些数据表明，TET诱导的髓鞘水肿中的初始基因事件是MBP转录本受到刺激。
