DIFFERENCES IN NIGRAL NEURON NUMBER AND SENSITIVITY TO 1-METHYL-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE IN C57/BL AND CD-1 MICE
DIFFERENCES IN NIGRAL NEURON NUMBER AND SENSITIVITY TO 1-METHYL-PHENYL-1,2,3,6-TETRAHYDROPYRIDINE IN C57/BL AND CD-1 MICE
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DOI：
10.1006/exnr.1994.1058
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发表时间：
1994-04-01
影响因子：
5.3
通讯作者：
PRZEDBORSKI, S
中科院分区：
文献类型：
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作者：
MUTHANE, U;RAMSAY, KA;PRZEDBORSKI, S
本研究表明，神经毒素1-甲基-4-苯基-1，2，3，6-四氢吡啶（MPTP）导致C57/bl小鼠纹状体多巴胺水平的显著下降幅度大于CD-1小鼠，从而证实了C57/bl小鼠对MPTP的更大敏感性。为了确定这两种小鼠品系之间MPTP敏感性差异的可能原因，我们使用酪氨酸羟化酶（TH）和钙结合蛋白-D-28 k（钙结合蛋白）的免疫染色比较了C57/BL和CD-1小鼠中MPTP的主要靶点黑质（SN）神经元的组织和数量。在盐水注射的动物中，有一个显着较低的SN TH阳性和钙结合蛋白阳性神经元的数量在C57/BL比CD-1小鼠，这些神经元的数量没有显着差异，发现在腹侧被盖区之间的两个菌株。在注射MPTP的动物中，SN TH阳性神经元的减少在C57/bl中比在CD-1小鼠中显著更大。相比之下，MPTP不会引起任何显着的变化，在任何应变的SN钙结合蛋白阳性神经元的数量。本研究表明，具有较少SN TH阳性神经元的C57/bl小鼠比CD-1小鼠对MPTP诱导的毒性更敏感。这一观察结果表明SN TH阳性神经元数量和MPTP敏感性之间可能存在负相关关系。如果正确的话，这一假设可能对帕金森病具有重大意义，因为这表明处于发展这种神经退行性疾病风险中的个体可能具有较低数量的SN TH阳性神经元。本研究还表明，SN钙结合蛋白阳性神经元的数量并不占这两个小鼠品系之间的MPTP的敏感性差异。(C)1994年出版社出版。
The present study demonstrates that the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) causes significantly greater reductions in striatal dopamine levels in C57/bl mice than in CD-1 mice, thus confirming a greater sensitivity of the C57/bl mice to MPTP. To determine the possible reasons for this difference in MPTP sensitivity between these two mouse strains, we have compared both the organization and the number of substantia nigra (SN) neurons, the primary target of MPTP, in C57/bl and in CD-1 mice using immunostaining for tyrosine hydroxylase (TH) and calbindin-D-28k (calbindin). In saline-injected animals, there is a significantly lower number of SN TH-positive and calbindin-positive neurons in C57/bl than CD-1 mice; no significant differences in the numbers of these neurons are found in the ventral tegmental area between the two strains. In MPTP-injected animals, the reductions in SN TH-positive neurons are significantly greater in C57/bl than in CD-1 mice. In contrast, MPTP does not cause any significant changes in the numbers of SN calbindin-positive neurons in either strain. The present study shows that C57/bl mice which have fewer SN TH-positive neurons are more sensitive to MPTP-induced toxicity than CD-1 mice. This observation suggests a possible inverse relationship between SN TH-positive neuron number and MPTP sensitivity. If correct, this hypothesis may be of major importance for Parkinson's disease since it is suggested that individuals at risk of developing this neurodegenerative disorder may have lower numbers of SN TH-positive neurons to start with. The present study also shows that SN calbindin-positive neuron numbers does not account for the differential sensitivity to MPTP between these two mouse strains. (C) 1994 Academic Press, Inc.