Neurodegeneration in autoimmune MRL-lpr mice as revealed by Fluoro Jade B staining
Neurodegeneration in autoimmune MRL-lpr mice as revealed by Fluoro Jade B staining
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DOI：
10.1016/s0006-8993(02)03980-x
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发表时间：
2003-02-28
期刊：
影响因子：
2.9
通讯作者：
Sakic, B
中科院分区：
文献类型：
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作者：
Ballok, DA;Millward, JM;Sakic, B
与许多患有红斑狼疮的人一样，Fas缺陷型MRL-lpr小鼠中全身性自身免疫和炎症的发展伴随着病因不明的CNS功能障碍。实验研究表明，淋巴细胞浸润到脉络丛，减少神经元的复杂性，延缓脑生长，脑室扩大。此外，脑室周围区域中具有缺口DNA的细胞（TUNEL+细胞）的存在增加表明MRL-1 pr小鼠脑细胞的加速凋亡。然而，缺乏死亡细胞是神经元的直接证据。为此目的，我们目前使用Fluoro-Jade B（FJB），一种对垂死神经元（凋亡和坏死两者）具有高亲和力的新型荧光染料。正如预期的那样，与对照组相比，患病的5个月大的MRL-lpr小鼠的大脑在皮质和脑室周围区域显示出增加的FJB阳性（+）细胞数量。FJB+细胞比TUNEL+细胞显著更多，并且仅约7%与TUNEL共定位。CD 4和CD 8标记物的免疫染色与FJB+细胞的数量无关，表明T淋巴细胞浸润到脑组织中不是神经元死亡的可靠预测因子。相反，全身性自身免疫的指数（脾肿大和高血清抗核抗体水平）与自身免疫性MRL-1 pr小鼠脑中FJB+细胞数量增加相关，支持自身免疫和神经变性之间的因果关系。综上所述，上述结果表明，T细胞浸润以外的因素和Fas介导的细胞凋亡以外的细胞死亡机制主导了狼疮易感MRL-lpr小鼠的神经元变性。(C)2002 Elsevier Science B. V.保留所有权利。
As in many humans suffering from lupus erythematosus, the development of systemic autoimmunity and inflammation in Fas-deficient MRL-lpr mice is accompanied by CNS dysfunction of unknown etiology. Experimental studies revealed infiltration of lymphoid cells into the choroid plexus, reduced neuronal complexity, retarded brain growth, and enlargement of cerebral ventricles. Moreover, an increased presence of cells with nicked-DNA (TUNEL+ cells) in the periventricular areas suggested accelerated apoptosis in brain cells of MRL-lpr mice. However, direct evidence that the dying cells were neurons was lacking. For this purpose, we presently use Fluoro-Jade B (FJB), a novel fluorescent dye which has high affinity for dying neurons (both apoptotic and necrotic). As expected, in comparison to the control groups, the brains of diseased, 5-month-old MRL-lpr mice showed increased numbers of FJB-positive (+) cells in cortical and periventricular regions. The FJB+ cells were significantly more numerous than TUNEL+ cells, and only -7% co-localized with TUNEL. Immunostaining for CD4 and CD8 markers did not correlate with the number of FJB+ cells, suggesting that T-lymphocyte infiltration into the brain tissue is not a reliable predictor of neuronal demise. Conversely, indices of systemic autoimmunity (splenomegaly and high serum anti-nuclear antibody levels) were associated with increased FJB+ cell numbers in brains of autoimmune MRL-lpr mice, supporting the causal link between autoimmunity and neurodegeneration. Taken together, the above results suggest that factors other than T-cell infiltration and cell death mechanisms other than Fas-mediated apoptosis dominate neuronal degeneration in lupus-prone MRL-lpr mice. (C) 2002 Elsevier Science B.V. All rights reserved.