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首页> 外文期刊>Epilepsia: Journal of the International League against Epilepsy >A cellular mechanism for dendritic spine loss in the pilocarpine model of status epilepticus.
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A cellular mechanism for dendritic spine loss in the pilocarpine model of status epilepticus.

机译：树突棘丧失的癫痫持续状态的毛果芸香碱模型中的一种细胞机制。

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PURPOSE: Previous studies have documented a synaptic translocation of calcineurin (CaN) and increased CaN activity following status epilepticus (SE); however, the cellular effect of these changes in CaN in the pathology of SE remains to be elucidated. This study examined a CaN-dependent modification of the dendritic cytoskeleton. CaN has been shown to induce dephosphorylation of cofilin, an actin depolymerization factor. The ensuing actin depolymerization can lead to a number of physiological changes that are of interest in SE. METHODS: SE was induced by pilocarpine injection, and seizure activity was monitored by video-EEG. Subcellular fractions were isolated by differential centrifugation. CaN activity was assayed using a paranitrophenol phosphate (pNPP) assay protocol. Cofilin phosphorylation was assessed using phosphocofilin-specific antibodies. Cofilin-actin binding was determined by coimmunoprecipitation, and actin polymerization was measured using a triton-solubilization protocol. Spines were visualized using a single-section rapid Golgi impregnation procedure. RESULTS: The immunoreactivity of phosphocofilin decreased significantly in hippocampal and cortical synaptosomal samples after SE. SE-induced cofilin dephosphorylation could be partially blocked by the preinjection of CaN inhibitors. Cofilin activation could be further demonstrated by increased actin-cofilin binding and a significant depolymerization of neuronal actin, both of which were also blocked by CaN inhibitors. Finally, we demonstrated a CaN-dependent loss of dendritic spines histologically. DISCUSSION: The data demonstrate a CaN-dependent, cellular mechanism through which prolonged seizure activity results in loss of dendritic spines via cofilin activation. Further research into this area may provide useful insights into the pathology of SE and epileptogenic mechanisms.
机译：目的：以前的研究已经证明了钙调神经磷酸酶（CaN）的突触易位和癫痫持续状态（SE）后CaN活性的增加;然而，这些变化在SE病理中的CaN的细胞作用仍有待阐明。这项研究检查了依赖CaN的树突状细胞骨架的修饰。 CaN已显示可诱导肌动蛋白解聚因子cofilin的去磷酸化。随后发生的肌动蛋白解聚反应可导致SE中引起许多生理变化。方法：通过毛果芸香碱注射诱导SE，并通过视频脑电图监测癫痫发作活动。通过差速离心分离亚细胞级分。 CaN活性使用对硝基苯酚磷酸酯（pNPP）测定方案进行测定。使用磷酸丝素蛋白特异性抗体评估了丝素蛋白的磷酸化。通过共免疫沉淀确定Cofilin-肌动蛋白的结合，并使用Triton增溶方案测量肌动蛋白的聚合。使用单节快速高尔基浸渍程序将脊柱可视化。结果：SE后海马和皮层突触体样品中磷纤蛋白的免疫反应性明显降低。 SE诱导的cofilin去磷酸化可以被CaN抑制剂的预注射部分阻止。肌动蛋白-肌动蛋白的结合增加和神经元肌动蛋白的显着解聚可以进一步证明肌动蛋白的激活，这两者也都被CaN抑制剂阻断。最后，我们在组织学上证实了CaN依赖性树突棘的丢失。讨论：数据证明了CaN依赖性的细胞机制，通过这种机制，延长的癫痫发作活动会通过cofilin激活导致树突棘丧失。对该领域的进一步研究可能会为SE和癫痫发生机制的病理学提供有用的见识。

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