NEONATAL EXPOSURE TO PARAQUAT OR MPTP INDUCES PERMANENT CHANGES IN STRIATUM DOPAMINE AND BEHAVIOR IN ADULT MICE
NEONATAL EXPOSURE TO PARAQUAT OR MPTP INDUCES PERMANENT CHANGES IN STRIATUM DOPAMINE AND BEHAVIOR IN ADULT MICE
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DOI：
10.1006/taap.1993.1194
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发表时间：
1993-10-01
影响因子：
3.8
通讯作者：
ERIKSSON, P
中科院分区：
文献类型：
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作者：
FREDRIKSSON, A;FREDRIKSSON, M;ERIKSSON, P
我们最近报道了环境毒物，如滴滴涕、多氯联苯、拟除虫菊酯和尼古丁，可以诱导成年小鼠永久性的功能和神经化学变化，在大脑快速生长的高峰期给予新生小鼠。本研究研究了新生儿暴露于百草枯（N,N ' -二甲基-4,4 ' -联吡啶）后的神经毒性作用。百草枯是一种结构类似于1-甲基-4-苯基吡啶离子（MPP+）的广谱除草剂，是诱发帕金森综合征的1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的活性代谢物。五组小鼠分别口服百草枯或MPTP: 1组，载药；2、3组，MPTP 0.3、20 mg/kg；第4、5组，百草枯0.07、0.36 mg/kg， 10、11日龄。给予百草枯0.36 mg/kg体重的小鼠，在第18天进行新生儿自发运动活动测试。在60天和120天进行成人自发运动活动测试。第125天处死小鼠，分析纹状体多巴胺（DA）、5-羟色胺（5-HT）及代谢物的含量。结果可总结如下：(1)各组均未出现急性毒性症状或体重增加差异。在给予百草枯0.36 mg/kg体重的小鼠中，在第18天也没有出现明显的呼吸窘迫或运动功能障碍。(2)60日龄时的行为测试显示，给予百草枯（两种剂量）和MPTP（两种剂量）的小鼠出现了明显的活动障碍。(3)在120天龄时，这种低活动行为持续存在，并且表现得更加明显。(4)大剂量MPTP和百草枯降低纹状体中DA和代谢物含量，但不影响5-羟色胺，而低剂量的MPTP和百草枯降低纹状体中DA和代谢物含量的程度较低。本研究中新生纹状体的行为改变，以及DA和代谢物的剂量依赖性减少，进一步证明了新生儿期对低剂量环境污染物的易感。
We have recently reported that environmental toxicants, such as DDT, PCBs, pyrethroids, and nicotine can induce permanent functional and neurochemical changes in adult mice when given to neonatal mice during the peak of rapid brain growth. In the present investigation the neurotoxic effects following neonatal exposure to paraquat (N,N′-dimethyl-4,4′-bipyridylium), a broad-spectrum herbicide with structural similarity to the 1-methyl-4-phenylpyridium ion (MPP+), the active metabolite of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) which can induce Parkinson′s syndrome, and MPTP were studied. Five groups of mice were given paraquat or MPTP orally: group 1, vehicle; groups 2 and 3, MPTP 0.3 and 20 mg/kg; groups 4 and 5, paraquat 0.07 and 0.36 mg/kg when 10 and 11 days old. Neonatal spontaneous motor activity was tested on Day 18 in mice given paraquat 0.36 mg/kg body wt. Adult spontaneous motor activity testing was performed at ages 60 and 120 days. On Day 125 the mice were decapitated and the contents of dopamine (DA), serotonin (5-HT), and metabolites in striatum were analyzed. The results may be summarized as follows: (1) No signs of acute toxicity or differences in weight gain were observed in any of the groups. Nor was any respiratory distress or motor performance dysfunction evident on Day 18 in mice given paraquat 0.36 mg/kg body wt. (2) The behavioral tests at 60 days of age showed a marked hypoactive condition in the mice given paraquat (at both doses) and MPTP (at both doses). (3) At the age of 120 days the hypoactive behavior persisted and appeared even more pronounced. (4) The high doses of MPTP and paraquat-and to a less extent the low doses-reduced the striatal content of DA and metabolites without affecting 5-HT. The altered behavior, together with the dose-dependent reduction of DA and metabolites in neostriata in this study, further demonstrates the susceptibility to low-dose exposure to environmental pollutants during the neonatal period.