Pérez-Otaño I, Luquin M R, Oset C, Herrero M T, Kupsch A, Oertel W, Obeso J A, Del Río J
Department of Pharmacology, University of Navarra, Medical School, Pamplona, Spain.
Exp Neurol. 1995 Jan;131(1):108-13. doi: 10.1016/0014-4886(95)90012-8.
The neurotoxicity induced by incidental prenatal exposure to 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) was studied in three marmosets. The baby marmosets exposed in utero to MPTP looked normal in the first few weeks of life but around 8 to 10 weeks of life they started to behave abnormally and were sacrificed when they were 20 weeks old. A marked reduction in DA levels was found in the baby marmosets prenatally exposed to MPTP as compared to the corresponding age-matched controls and this was highly significant in the caudate nucleus, putamen, and nucleus accumbens. Serotonin content was normal in the caudate and putamen and was only significantly reduced in the nucleus accumbens, hypothalamus, and cingulate cortex. Met-enkephalin levels were reduced in the caudate nucleus, putamen, and globus pallidus. Substance P content tended to be lower in all regions examined; however, the decrease was only statistically significant in the substantia nigra. These results indicate that prenatal exposure to MPTP induces a marked and long-lasting alteration in monoaminergic and peptidergic systems of the primate brain. This observation may provide a new insight into the role of toxins in the etiology of Parkinson's disease.
在三只狨猴中研究了孕期意外接触1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）所诱发的神经毒性。子宫内接触MPTP的幼龄狨猴在出生后的最初几周看起来正常，但在8至10周龄左右开始出现行为异常，并在20周龄时被处死。与相应年龄匹配的对照组相比，产前接触MPTP的幼龄狨猴中多巴胺（DA）水平显著降低，这在尾状核、壳核和伏隔核中尤为明显。尾状核和壳核中的5-羟色胺含量正常，仅在伏隔核、下丘脑和扣带回皮质中显著降低。脑啡肽水平在尾状核、壳核和苍白球中降低。在所检查的所有区域中，P物质含量均有降低趋势；然而，仅在黑质中这种降低具有统计学意义。这些结果表明，产前接触MPTP会导致灵长类动物大脑单胺能和肽能系统发生显著且持久的改变。这一观察结果可能为毒素在帕金森病病因学中的作用提供新的见解。
