Susceptibility to excitotoxic and metabolic striatal neurodegeneration in the mouse is genotype dependent.
Susceptibility to excitotoxic and metabolic striatal neurodegeneration in the mouse is genotype dependent.
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小鼠对兴奋性毒性和代谢性纹状体神经变性的易感性是基因型依赖性的。
DOI：
10.1016/j.brainres.2005.01.067
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发表时间：
2005
期刊：
影响因子：
--
通讯作者：
Schauwecker,PaulaElyse
中科院分区：
文献类型：
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作者：
Schauwecker,PaulaElyse
先前，我们已经报道了海马对兴奋毒素施用的神经毒性作用的易感性是应变依赖性的[Schauwecker和Steward，Proc.Natl. Acad. Sci. U.S.A.94（1997）4103]。然而，目前尚不清楚菌株相关的基因产物是否可能在提供对产生纹状体病变的药物的保护方面发挥类似的作用。本系列实验旨在阐明遗传背景是否改变代谢或兴奋性损伤后纹状体内神经元的活力。因此，我们已经研究了使用充分表征的亨廷顿病动物模型的小鼠品系对纹状体损伤的易感性的影响，通过检查先前被鉴定为对兴奋性毒素诱导的海马细胞死亡具有抗性的C57 BL/6小鼠是否对喹啉酸、丙二酸和3-硝基丙酸（3-NP）具有抗性。纹状体内注射丙二酸酯或喹啉酸酯和全身给予3-NP导致C57 BL/6小鼠的纹状体病变明显小于FVB/N小鼠，FVB/N小鼠先前被鉴定为对海马兴奋性毒性损伤敏感。纹状体病变的抵抗力下降的动物品系的存在表明，有介导的因素参与纹状体的优先脆弱性神经毒性病变。这些因素的识别可以为亨廷顿病的治疗干预提供策略。
Previously, we had reported that hippocampal susceptibility to the neurotoxic effects of excitotoxin administration is strain dependent [Schauwecker and Steward, Proc. Natl. Acad. Sci. U.S.A. 94 (1997) 4103]. However, it has been unclear whether strain-related gene products may play a similar role in providing protection against drugs that produce striatal lesions. The present series of experiments sought to elucidate whether genetic background alters neuronal viability within the striatum following metabolic or excitotoxic injury. Thus, we have examined the effect of mouse strain on susceptibility to striatal injury using well-characterized animal models of Huntington's disease by examining whether C57BL/6 mice, previously identified as resistant to excitotoxin-induced hippocampal cell death, are resistant to quinolinate, malonate, and 3-nitropropionic acid (3-NP). Intrastriatal injection of either malonate or quinolinate and systemic administration of 3-NP resulted in significantly smaller striatal lesions in C57BL/6 mice as compared to FVB/N mice, previously identified as susceptible to hippocampal excitotoxic injury. The existence of an animal strain with decreased resistance to striatal lesions suggests that there are mediating factors involved in the preferential vulnerability of the striatum to neurotoxic lesioning. The identification of these factors could provide strategies for therapeutic intervention in Huntington's disease.