He Yan, Akumuo Rita C, Yang Yuan, Hewett Sandra J
Department of Biology, Program in Neuroscience, Syracuse University, Syracuse, NY 13210, United States.
Department of Biology, Program in Neuroscience, Syracuse University, Syracuse, NY 13210, United States.
Neurosci Lett. 2017 Mar 16;643:65-69. doi: 10.1016/j.neulet.2017.02.031. Epub 2017 Feb 14.
Considerable evidence supports a contributory role for leukocyte-type 12/15 Lipoxygenase (L-12/15 LO) in mediating hippocampal and cortical neuronal injury in models of Alzheimer's disease and stroke. Whether L-12/15 LO contributes to neuronal injury in a model of Huntington's disease (HD) has yet to be determined. HD is characterized by marked striatal neuronal loss, which can be mimicked in humans and animals by inhibition of mitochondrial complex II using 3-Nitropropionic acid (3-NP). Herein, we compared histological and behavioral outcomes between mice that were wild-type or null for L-12/15 LO following systemic injection of 3NP. We found that mice deficient in L-12/15 LO had a higher incidence of striatal lesions coincident with an increase in morbidity as compared to their wild-type littermate controls. This could not be explained by differential metabolism of 3-NP as striatal succinate dehydrogenase activity was inhibited to the same extent in both genotypes. The present results show that deleting L-12/15 LO is detrimental to the striatum in the setting of chronic, systemic 3-NP exposure and are consistent with the overall conclusion that region-specific effects may determine the ultimate outcome of L-12/15 LO activation in the setting of brain injury.
大量证据支持白细胞型12/15脂氧合酶（L-12/15 LO）在阿尔茨海默病和中风模型中介导海马和皮质神经元损伤方面发挥作用。L-12/15 LO是否在亨廷顿舞蹈病（HD）模型中导致神经元损伤尚未确定。HD的特征是纹状体神经元显著丧失，在人类和动物中可通过使用3-硝基丙酸（3-NP）抑制线粒体复合物II来模拟。在此，我们比较了全身注射3-NP后野生型或L-12/15 LO基因敲除小鼠的组织学和行为学结果。我们发现，与野生型同窝对照相比，L-12/15 LO基因缺陷小鼠纹状体损伤的发生率更高，同时发病率增加。这不能用3-NP的代谢差异来解释，因为两种基因型的纹状体琥珀酸脱氢酶活性受到的抑制程度相同。目前的结果表明，在慢性全身暴露于3-NP的情况下，删除L-12/15 LO对纹状体有害，这与区域特异性效应可能决定脑损伤情况下L-12/15 LO激活的最终结果这一总体结论一致。
