TRANSPLACENTAL EFFECT OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) ON BRAIN DOPAMINERGIC-NEURONS IN THE MOUSE - AN IMMUNOHISTOCHEMICAL STUDY
TRANSPLACENTAL EFFECT OF 1-METHYL-4-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE (MPTP) ON BRAIN DOPAMINERGIC-NEURONS IN THE MOUSE - AN IMMUNOHISTOCHEMICAL STUDY
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DOI：
10.1007/bf00294662
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发表时间：
1989-01-01
影响因子：
12.7
通讯作者：
NAGATSU, I
中科院分区：
文献类型：
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作者：
FURUNE, S;MIURA, K;NAGATSU, I
对单胺神经元进行免疫组织化学研究，以评估 1-甲基-4-苯基-1,2,3,6-四氢吡啶 (MPTP) 对年轻成年小鼠的毒性作用，并与其后代进行比较。 9-11周龄小鼠（C57BL/6J）在妊娠第9天和第12天（G9和G12）皮下注射大剂量MPTP（每天17mg/kg）流产，并在13周龄时进行检查。相反，在怀孕期间连续接受低剂量 MPTP（G9-G17 每天 2.8 mg/kg，持续 8 天）的小鼠成功分娩，并在 15 周龄时进行检查。对 1 周和 6 周龄的小小鼠进行了检查。与对照组相比，接受高剂量 MPTP 治疗的 13 周龄小鼠尾壳核的酪氨酸羟化酶、芳香族 L-氨基酸脱羧酶和多巴胺 (DA) 免疫反应密度有所降低，但暴露于低剂量 MPTP 的 15 周龄小鼠的尾壳核免疫反应密度则没有降低。尾壳核的 DA 免疫反应密度是 1 周和 6 周龄幼鼠中唯一减少的染色。总之，这些结果表明，注射给怀孕小鼠的 MPTP 会导致其后代纹状体中的 DA 消耗，表明 MPTP 具有跨胎盘效应。研究结果还表明，胎儿大脑比年轻怀孕小鼠的大脑更容易受到 MPTP 毒性的影响。
Immunohistochemical studies of monoamine neurons were performed to evaluate toxic effects of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) on young adult mice and compare them with those of their offspring. Mice, 9-11 weeks old (C57BL/6J), injected subcutaneously with a large dose of MPTP (17 mg/kg per day) during pregnancy on Day 9 and 12 of gestation (G9 and G12) miscarried and were examined at 13 weeks of age. Conversely, mice treated during pregnancy with sequential low dose of MPTP (2.8 mg/kg per day at G9-G17 for 8 days) successfully delivered their babies and were examined at the age of 15 weeks. Baby mice were examined at 1 and 6 weeks of age. The tyrosine hydroxylase-, aromatic L-amino acid decarboxylase- and dopamine (DA)-immunoreactive density of caudoputamen was reduced in 13-week-old mice treated with high dose of MPTP but not in the 15-week-old mothers exposed to a low dose of MPTP as compared to their respective controls. The DA-immunoreactive density of the caudoputamen was the only staining that was reduced in both 1- and 6-week-old baby mice. In conclusion, these results demonstrate that MPTP injected to pregnant mice causes a DA depletion in the striatum of their offspring indicating a transplacental effect of MPTP. The findings also indicate that fetal brain is more susceptible to MPTP toxicity than the brain of young pregnant mice.