Adeyemo O M, Youdim M B, Markey S P, Markey C J, Pollard H B
Laboratory of Cell Biology and Genetics, N.I.D.D.K., National Institute of Health, Bethesda, MD 20892.
Eur J Pharmacol. 1993 Aug 24;240(2-3):185-93. doi: 10.1016/0014-2999(93)90897-q.
Administration of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to the goldfish causes a reversible, Parkinson's disease-like syndrome which includes loss of noradrenaline and dopamine from the brain, accumulation of the toxic metabolite 1-methyl-4-phenylpyridinium species (MPP+), and substantial reduction in movement. L-Deprenyl, a selective monoamine oxidase-B inhibitor, protects the goldfish from loss of movement, but clorgyline, a selective monoamine oxidase-A inhibitor, has no such protective action. L-Deprenyl and clorgyline primarily inhibit goldfish brain monoamine oxidase-B and monoamine oxidase-A, respectively. The mechanism by which MPTP causes reduced movement in goldfish is to cause an increase in resting time. Otherwise normal average velocity occurred during periods of movement. L-Deprenyl protection results in entirely 'normal' levels of resting time and average velocity during times of movement. Equivalent observations regarding l-deprenyl and clorgyline have been made in primate models of MPTP toxicity, and l-deprenyl is used for treatment of Parkinson's disease in humans. Therefore it is suggested that the evolutionarily equivalent subcortical circuitry and neural density of the goldfish brain may provide a useful model upon which to search for drugs relevant to human Parkinson's disease.
给金鱼注射1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）会导致一种可逆的、类似帕金森病的综合征，其中包括大脑中去甲肾上腺素和多巴胺的丧失、有毒代谢物1-甲基-4-苯基吡啶离子（MPP+）的积累以及运动能力的显著下降。L-司来吉兰，一种选择性单胺氧化酶-B抑制剂，可保护金鱼不出现运动能力丧失，但氯吉兰，一种选择性单胺氧化酶-A抑制剂，则没有这种保护作用。L-司来吉兰和氯吉兰分别主要抑制金鱼脑中的单胺氧化酶-B和单胺氧化酶-A。MPTP导致金鱼运动能力下降的机制是使静息时间增加。在运动期间，平均速度在其他方面是正常的。L-司来吉兰的保护作用导致运动期间的静息时间和平均速度完全处于“正常”水平。在MPTP毒性的灵长类动物模型中也观察到了关于L-司来吉兰和氯吉兰的类似情况，并且L-司来吉兰被用于治疗人类的帕金森病。因此，有人提出金鱼脑在进化上等效的皮层下神经回路和神经密度可能提供一个有用的模型，用于寻找与人类帕金森病相关的药物。
