Albanese A, Granata R, Gregori B, Piccardi M P, Colosimo C, Tonali P
Istituto di Neurologia, Università Cattolica del Sacro Cuore, Roma, Italy.
Neuroscience. 1993 Aug;55(3):823-32. doi: 10.1016/0306-4522(93)90444-k.
The behavioural, biochemical and morphological effects of a chronic administration of low doses of 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) were studied in the common marmoset. Monkeys received the toxin (1 mg/kg i.p.) twice a week for four months. Group A monkeys were studied one week after the last injection of MPTP; group B monkeys were studied eight months after the last toxic injection. The monkey behaviour was observed throughout the experiment; the biochemical and morphological correlates were studied post mortem in the neostriatum and in the substantia nigra, respectively. Data collected from MPTP-treated marmosets were compared to those obtained from sham-injected control monkeys. The results can be summarized as follows. (1) In all MPTP-treated marmosets a progressive Parkinsonism occurred. In group B monkeys, a gradual behavioural recovery was observed after MPTP was discontinued. (2) Biochemical analysis of group A marmosets showed a depletion of dopamine, of 3,4-hydroxyphenylacetic acid and of homovanillic acid, and no variations in dopamine turnover in the neostriatum of MPTP-treated marmosets. In group B, biochemical analysis showed no differences between controls and MPTP-treated animals. (3) Morphological analysis showed that the density of midbrain dopaminergic neurons located in the substantia nigra was unchanged in group A monkeys, but was reduced by 6.8% in MPTP-treated monkeys of group B. The measurement of cross-sectional area showed that midbrain dopaminergic neurons were swollen in MPTP-treated monkeys of group A, with a 11.0% increase of cell size as compared to controls. In group A the nuclei were also swollen, being 304.8% larger in MPTP-treated monkeys, with a nucleus-to-cytoplasm ratio of 65.9% (as compared to 34.0% of controls). In group B monkeys cell size was increased by 18.4% in MPTP-treated marmosets, but the nuclei were of comparable size. The present data show that a chronic administration of low doses of MPTP brings about biochemical and morphological abnormalities. The first occur acutely in terminals and are reverted early after discontinuance of exposure to the toxin; the latter occur in dopaminergic perikarya, last longer than biochemical abnormalities and, at variance with them, increase in severity after MPTP is discontinued. Morphological abnormalities include early events, such as a transient swelling of nuclei or a long-lasting swelling of neurons, and late events, such as a decrease in the number of tyrosine hydroxylase-positive perikarya.(ABSTRACT TRUNCATED AT 400 WORDS)
在普通狨猴中研究了长期低剂量给予1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）的行为、生化和形态学影响。猴子每周两次腹腔注射毒素（1mg/kg），持续四个月。A组猴子在最后一次注射MPTP一周后进行研究；B组猴子在最后一次毒素注射八个月后进行研究。在整个实验过程中观察猴子的行为；分别在新纹状体和黑质中对生化和形态学相关性进行死后研究。将MPTP处理的狨猴收集的数据与假注射对照猴子获得的数据进行比较。结果可总结如下。（1）在所有MPTP处理的狨猴中均出现进行性帕金森病。在B组猴子中，停止使用MPTP后观察到行为逐渐恢复。（2）A组狨猴的生化分析显示多巴胺、3,4-二羟基苯乙酸和高香草酸耗竭，且MPTP处理的狨猴新纹状体中的多巴胺周转率无变化。在B组中，生化分析显示对照组和MPTP处理动物之间无差异。（3）形态学分析表明，A组猴子中位于黑质的中脑多巴胺能神经元密度未改变，但B组MPTP处理的猴子中该密度降低了6.8%。横截面积测量显示，A组MPTP处理的猴子中脑多巴胺能神经元肿胀，与对照组相比细胞大小增加了11.0%。在A组中，细胞核也肿胀，MPTP处理的猴子中细胞核比对照组大304.8%，核质比为65.9%（对照组为34.0%）。在B组猴子中，MPTP处理的狨猴细胞大小增加了18.4%，但细胞核大小相当。目前的数据表明，长期低剂量给予MPTP会导致生化和形态学异常。前者在终末急性发生，并在停止接触毒素后早期恢复；后者发生在多巴胺能神经元胞体，持续时间比生化异常长，并且与生化异常不同的是，在停止使用MPTP后严重程度增加。形态学异常包括早期事件，如细胞核的短暂肿胀或神经元的长期肿胀，以及晚期事件，如酪氨酸羟化酶阳性胞体数量的减少。（摘要截断于400字）
