Mailman R B, Krigman M R, Frye G D, Hanin I
J Neurochem. 1983 May;40(5):1423-9. doi: 10.1111/j.1471-4159.1983.tb13585.x.
The effects on brain neurochemistry of two neurotoxic tin compounds, trimethyltin (TMT) hydroxide and triethyltin (TET) sulfate, were examined. Long-Evans rats were treated with TMT hydroxide (1 mg/kg, i.p.) on alternate days from day 2 to 29 of life. These treatments caused a weight deficit of 10-20% by the time the animals were killed on day 55 by head-focused microwave irradiation. These TMT treatments are known to cause severe neuronal loss in the hippocampus and lesser damage in other brain regions. Accordingly, the concentration of gamma-aminobutyric acid (GABA) was decreased in the hippocampus; however, acetylcholine and choline concentrations were unaffected. These data suggest that TMT-induced effects on GABA systems are greater than that due simply to generalized neuronal loss. The TMT treatments also caused a significant decrease in dopamine concentrations in the striatum, but did not alter the concentrations of dihydroxyphenylacetic acid or homovanillic acid, the acidic metabolites of dopamine. Conversely, concentrations of dopamine and norepinephrine in the brain stem and norepinephrine in the cerebellum were not altered. Despite reports in the literature of TMT-induced neuronal damage in areas of the cortex, no effects on GABA, acetylcholine, or choline levels were found in the cortical areas examined, or in the hypothalamus. TET sulfate (0.3 mg/kg/day) was administered for 6 consecutive days of every week during days 2-29 of life. This dose is lower than that needed to cause intramyelin edema, yet it does result in long-term behavioral changes. Despite this, no changes in the concentration of any of the measured neurotransmitters or their metabolites were detected. In concert, these data demonstrate that neurochemical methods should not be used as neurological "screens," but rather to define specific mechanisms suggested by detailed behavior, pharmacological, and/or physiological studies.
研究了两种神经毒性锡化合物——氢氧化三甲基锡（TMT）和硫酸三乙基锡（TET）对脑内神经化学的影响。从出生后第2天至29天，Long-Evans大鼠每隔一天接受一次氢氧化三甲基锡（1 mg/kg，腹腔注射）处理。到第55天通过头部聚焦微波照射处死动物时，这些处理导致动物体重减轻10 - 20%。已知这些TMT处理会导致海马体中严重的神经元损失，而对其他脑区的损伤较小。因此，海马体中γ-氨基丁酸（GABA）的浓度降低；然而，乙酰胆碱和胆碱的浓度未受影响。这些数据表明，TMT对GABA系统的影响大于单纯因神经元普遍损失所导致的影响。TMT处理还导致纹状体中多巴胺浓度显著降低，但未改变多巴胺的酸性代谢产物二羟基苯乙酸或高香草酸的浓度。相反，脑干中的多巴胺和去甲肾上腺素浓度以及小脑中的去甲肾上腺素浓度未发生改变。尽管文献报道TMT会导致皮质区域神经元损伤，但在所检查的皮质区域或下丘脑未发现对GABA、乙酰胆碱或胆碱水平有影响。在出生后第2天至29天期间，每周连续6天给予硫酸三乙基锡（0.3 mg/kg/天）。该剂量低于引起髓鞘内水肿所需的剂量，但确实会导致长期行为改变。尽管如此，未检测到任何被测神经递质或其代谢产物的浓度有变化。综合来看，这些数据表明神经化学方法不应被用作神经学“筛查”，而应用于确定详细行为、药理学和/或生理学研究所提示的特定机制。
