Pollard H B, Kuijpers G A, Adeyemo O M, Youdim M B, Goping G
Laboratory of Cell Biology and Genetics, NIDDK, National Institutes of Health, Bethesda, Maryland 20892, USA.
Exp Neurol. 1996 Nov;142(1):170-8. doi: 10.1006/exnr.1996.0188.
The neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) can induce a parkinsonian syndrome in humans and nonhuman primates, which is susceptible to treatment and prevention by drugs such as L-DOPA and L-deprenyl. Recently, we have reported that MPTP can also cause a parkinsonian syndrome in the common goldfish, which appears to faithfully mirror the neurochemical and behavioral aspects of the action of MPTP in the higher vertebrates. In addition, we recently identified the likely teleost equivalent of the substantia nigra in the goldfish forebrain, the "nucleus pars medialis," on the basis of its destruction by MPTP and selective protection by the MAO-B blocker L-deprenyl. In the present work we substantiate this conclusion by examining tissue destruction the goldfish forebrain at increasing MPTP concentrations, up to the the LD50 of 200 mg/kg. In addition, we show that at the highest MPTP dose subtle changes also occur with low frequency in nondopaminergic cells in the optic tectum, and in ependymal cells lining the midbrain ventricle. The effects on ependymal cells are similar to those previously noted in the forebrain. We conclude that the goldfish model continues to faithfully mimic the histologic pattern of parkinsonian tissue destruction engendered by MPTP in primate models.
神经毒素1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）可在人类和非人类灵长类动物中诱发帕金森综合征，该综合征易受左旋多巴和左旋司来吉兰等药物的治疗和预防。最近，我们报道MPTP也可在普通金鱼中引发帕金森综合征，这似乎如实地反映了MPTP在高等脊椎动物中作用的神经化学和行为方面。此外，我们最近基于金鱼前脑中被MPTP破坏以及被单胺氧化酶B（MAO-B）阻滞剂左旋司来吉兰选择性保护，确定了金鱼前脑中可能相当于黑质的结构，即“内侧核”。在本研究中，我们通过检查金鱼前脑在MPTP浓度不断增加直至200 mg/kg的半数致死量（LD50）时的组织破坏情况，证实了这一结论。此外，我们表明，在最高MPTP剂量下，视顶盖中的非多巴胺能细胞以及中脑脑室衬里的室管膜细胞也会低频发生细微变化。对视管膜细胞的影响与之前在前脑中观察到的相似。我们得出结论，金鱼模型继续如实地模拟了MPTP在灵长类动物模型中引发的帕金森组织破坏的组织学模式。
