Synuclein accumulation is associated with cell-specific neuronal death after spinal cord injury
Synuclein accumulation is associated with cell-specific neuronal death after spinal cord injury
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DOI：
10.1002/cne.23011
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发表时间：
2012-06-01
影响因子：
2.5
通讯作者：
Morgan, Jennifer R.
中科院分区：
文献类型：
--
作者：
Busch, David J.;Morgan, Jennifer R.
脊髓损伤会切断神经元，导致许多神经元死亡，而另一些神经元存活。因此，重要的是要确定的因素，导致神经元损伤后死亡的第一步，发展更好的策略，增加神经元的存活和功能恢复。然而，决定受损神经元存活或死亡的内在分子通路仍然令人惊讶地不清楚。为了解决这个问题，我们利用了大尺寸的巨型网状脊髓（RS）神经元的七鳃鳗，海岩鳗的大脑。我们报告说，巨大的RS神经元的轴突切断诱导他们的选择子集积累高水平的突触核蛋白，突触囊泡相关蛋白，其异常积累与帕金森氏病。损伤诱导的突触核蛋白积聚仅发生在通过组织学和Fluoro-Jade C染色被归类为较差存活者的神经元中。相比之下，损伤后突触核蛋白免疫荧光在被鉴定为良好存活者的神经元中保持在对照水平。突触核蛋白的积累出现在聚集的细胞内包涵体的形式。积累突触核蛋白的细胞也表现出更多的含有泛素的内含物，类似于疾病状态期间发生的情况。当在相同的神经元中测量突触核蛋白水平和细胞活力时，很明显突触核蛋白积累先于随后的神经元死亡并与随后的神经元死亡密切相关。因此，突触核蛋白积累被确定为轴突切断术后即将发生的神经元死亡的标志物和潜在风险因素，将其影响扩展到神经退行性疾病之外。J. Comp.神经元520：17511771，2012。(C)2011 Wiley Periodicals，Inc.
Spinal cord injury axotomizes neurons and induces many of them to die, whereas others survive. Therefore, it is important to identify factors that lead to neuronal death after injury as a first step toward developing better strategies for increasing neuronal survival and functional recovery. However, the intrinsic molecular pathways that govern whether an injured neuron lives or dies remain surprisingly unclear. To address this question, we took advantage of the large size of giant reticulospinal (RS) neurons in the brain of the lamprey, Petromyzon marinus. We report that axotomy of giant RS neurons induces a select subset of them to accumulate high levels of synuclein, a synaptic vesicle-associated protein whose abnormal accumulation is linked to Parkinson's disease. Injury-induced synuclein accumulation occurred only in neurons that were classified as poor survivors by both histological and Fluoro-Jade C staining. In contrast, post-injury synuclein immunofluorescence remained at control levels in neurons that were identified as good survivors. Synuclein accumulation appeared in the form of aggregated intracellular inclusions. Cells that accumulated synuclein also exhibited more ubiquitin-containing inclusions, similar to what occurs during disease states. When synuclein levels and cell vitality were measured in the same neurons, it became clear that synuclein accumulation preceded and strongly correlated with subsequent neuronal death. Thus, synuclein accumulation is identified as a marker and potential risk factor for forthcoming neuronal death after axotomy, expanding its implications beyond the neurodegenerative diseases. J. Comp. Neurol. 520:17511771, 2012. (C) 2011 Wiley Periodicals, Inc.