6-Hydroxydopamine as a tool to understand adaptive immune system-induced dopamine neurodegeneration in Parkinson's disease
6-Hydroxydopamine as a tool to understand adaptive immune system-induced dopamine neurodegeneration in Parkinson's disease
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DOI：
10.3109/08923973.2015.1070172
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发表时间：
2015-07
影响因子：
3.3
通讯作者：
S. Theodore;W. Maragos
中科院分区：
文献类型：
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作者：
S. Theodore;W. Maragos
摘要背景：神经免疫反应与帕金森病（PD）中人类黑质（SN）的神经变性相关。目的：探讨神经毒素6-羟基多巴胺（6-OHDA）可用作小鼠了解PD免疫反应的工具的可能性。材料和方法：采用6-OHDA单侧注射于小鼠黑质。在注射后1周、2周和4周，我们使用标记物Iba-1和gp 91 PHOX的免疫组织化学来研究SN中活化的小胶质细胞。为了检查适应性免疫应答，我们使用免疫组织化学检测CD 3阳性T淋巴细胞、CD 45 R阳性B淋巴细胞和抗小鼠免疫球蛋白G（IgG）。多巴胺神经元的损失进行了研究，使用免疫组织化学的多巴胺神经元标记物，酪氨酸羟化酶。结果如下：与溶媒相比，6-OHDA给药诱导SN中强烈的IgG沉积以及T-和B-淋巴细胞向中脑注射侧的浸润增加。在6-OHDA组的每个时间点，适应性免疫应答与多巴胺神经元的广泛破坏和广泛的小胶质细胞活化相关。结论：我们的研究结果表明，在小鼠中给予6-OHDA可以成为理解PD中适应性免疫激活诱导的神经变性的潜在机制的工具。
Abstract Context: Neuroimmunological response is associated with neurodegeneration in the human substantia nigra (SN) in Parkinson’s disease (PD). Objective: To explore the possibility that the neurotoxin, 6-hydroxydopamine (6-OHDA), could be used as a tool in mice to understand the immune response in PD. Materials and methods: We employed unilateral administration of 6-OHDA into the mouse SN. At 1 week, 2 weeks and 4 weeks post-injection, we used immunohistochemistry for the markers Iba-1 and gp91PHOX to investigate activated microglia in the SN. To examine the adaptive immune response, we used immunohistochemistry for CD3-positive T-lymphocytes, CD45R-positive B-lymphocytes and anti-mouse immunoglobulin-G (IgG). Dopamine neuron loss was examined using immunohistochemistry for the dopamine neuron marker, tyrosine hydroxylase. Results: Compared to vehicle, 6-OHDA administration induced an intense IgG deposition in the SN as well as increased infiltration of both T- and B- lymphocytes into the injected side of the midbrain. The adaptive immune response was associated with extensive destruction of dopamine neurons and extensive microglial activation at every time point in the 6-OHDA groups. Conclusion: Our results suggest that 6-OHDA administration in mice can a potential tool for understanding mechanisms underlying adaptive immune activation-induced neurodegeneration in PD.