Rcom-H'cheo-Gauthier Alexandre N, Davis Amelia, Meedeniya Adrian C B, Pountney Dean L
Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia.
Menzies Health Institute Queensland, School of Medical Science, Griffith University, Gold Coast, Queensland 4222, Australia.
Mol Cell Neurosci. 2016 Dec;77:65-75. doi: 10.1016/j.mcn.2016.10.003. Epub 2016 Oct 14.
α-Synuclein (α-syn) aggregates (Lewy bodies) in Dementia with Lewy Bodies (DLB) may be associated with disturbed calcium homeostasis and oxidative stress. We investigated the interplay between α-syn aggregation, expression of the calbindin-D28k (CB) neuronal calcium-buffering protein and oxidative stress, combining immunofluorescence double labelling and Western analysis, and examining DLB and normal human cases and a unilateral oxidative stress lesion model of α-syn disease (rotenone mouse). DLB cases showed a greater proportion of CB+ cells in affected brain regions compared to normal cases with Lewy bodies largely present in CB- neurons and virtually undetected in CB+ neurons. The unilateral rotenone-lesioned mouse model showed a greater proportion of CB+ cells and α-syn aggregates within the lesioned hemisphere than the control hemisphere, especially proximal to the lesion site, and α-syn inclusions occurred primarily in CB- cells and were almost completely absent in CB+ cells. Consistent with the immunofluorescence data, Western analysis showed the total CB level was 25% higher in lesioned compared to control hemisphere in aged animals that are more sensitive to lesion and 20% higher in aged compared to young mice in lesioned hemisphere, but not significantly different between young and aged in the control hemisphere. Taken together, the findings show α-syn aggregation is excluded from CB+ neurons, although the increased sensitivity of aged animals to lesion was not related to differential CB expression.
路易体痴呆（DLB）中α-突触核蛋白（α-syn）聚集体（路易小体）可能与钙稳态紊乱和氧化应激有关。我们结合免疫荧光双标记和蛋白质印迹分析，研究了α-syn聚集、钙结合蛋白-D28k（CB）神经元钙缓冲蛋白表达与氧化应激之间的相互作用，并检测了DLB患者、正常人类病例以及α-syn病单侧氧化应激损伤模型（鱼藤酮小鼠）。与正常病例相比，DLB病例在受影响脑区中CB阳性细胞比例更高，路易小体主要存在于CB阴性神经元中，而在CB阳性神经元中几乎未检测到。单侧鱼藤酮损伤小鼠模型显示，损伤半球内CB阳性细胞和α-syn聚集体的比例高于对照半球，尤其是在损伤部位附近，并且α-syn包涵体主要出现在CB阴性细胞中，在CB阳性细胞中几乎完全不存在。与免疫荧光数据一致，蛋白质印迹分析显示，在对损伤更敏感的老年动物中，损伤半球的总CB水平比对照半球高25%，在损伤半球中，老年小鼠比年轻小鼠高20%，但在对照半球中，年轻和老年小鼠之间没有显著差异。综上所述，研究结果表明α-syn聚集被排除在CB阳性神经元之外，尽管老年动物对损伤的敏感性增加与CB表达差异无关。
