Synapse loss induced by interleukin-1β requires pre- and post-synaptic mechanisms.
Synapse loss induced by interleukin-1β requires pre- and post-synaptic mechanisms.
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DOI：
10.1007/s11481-012-9342-7
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发表时间：
2012-09
影响因子：
6.2
通讯作者：
Thayer, Stanley A.
中科院分区：
文献类型：
--
作者：
Mishra, Anjuli;Kim, Hee Jung;Shin, Angela H.;Thayer, Stanley A.
白细胞介素-1 β（IL-1β）是一种对神经元功能和存活有显著影响的炎性细胞因子。在这里，我们研究了IL-1β对培养的大鼠海马神经元之间突触的影响，使用基于成像的测定来量化融合到绿色荧光蛋白的支架蛋白突触后密度95簇。用IL-1β处理24 h诱导突触位点数目减少23± 3%。药理学研究表明，突触丢失是由IL-1受体介导的，随后激活了两条通路。需要COX 2介导的前列腺素产生和Src家族酪氨酸激酶的突触后激活。突触前谷氨酸的释放和随后的NMDA受体的激活是IL-1β诱导的突触丢失所必需的。无论是Src激活或前列腺素E2（PGE 2）的应用单独是不够的，以减少突触的数量。然而，在表达组成性活性或突触活化Src的细胞中，PGE 2诱导突触丧失。因此，IL-1β通过同时激活需要突触前和突触后活性的多个通路来减少突触连接的数量。这些结果突出了可能证明对神经炎性疾病的药物治疗重要的靶点。
Interleukin-1β (IL-1β) is an inflammatory cytokine that exerts marked effects on neuronal function and survival. Here we examined the effects of IL-1β on synapses between rat hippocampal neurons in culture using an imaging-based assay to quantify clusters of the scaffolding protein postsynaptic density 95 fused to green fluorescent protein. Treatment with IL-1β for 24 h induced a 23±3 % loss in the number of synaptic sites. Pharmacological studies indicated that synapse loss was mediated by the IL-1 receptor with subsequent activation of two pathways. COX2-mediated prostaglandin production and postsynaptic activation of a Src family tyrosine kinase were required. Presynaptic release of glutamate with subsequent activation of NMDA receptors was necessary for IL-1β-induced synapse loss. Neither Src activation nor prostaglandin E2 (PGE2) application alone was sufficient to reduce the number of synapses. However, in cells expressing constitutively active or pharmacologically activated Src, PGE2 induced synapse loss. Thus, IL-1β reduces the number of synaptic connections by simultaneously activating multiple pathways that require both pre- and post-synaptic activity. These results highlight targets that may prove important for pharmacotherapy of neuroinflammatory disease.
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影响因子：
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作者：
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通讯作者：
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