Celsr2 Knockout Alleviates Inhibitory Synaptic Stripping and Benefits Motoneuron Survival and Axon Regeneration After Branchial Plexus Avulsion.
Celsr2 Knockout Alleviates Inhibitory Synaptic Stripping and Benefits Motoneuron Survival and Axon Regeneration After Branchial Plexus Avulsion.
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DOI：
10.1007/s12035-022-03198-3
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发表时间：
2023-04
影响因子：
5.1
通讯作者：
Zhou, Libing
中科院分区：
文献类型：
--
作者：
Yu, Lingtai;Liu, Mengfan;Li, Fuxiang;Wang, Qianghua;Wang, Meizhi;So, Kwok-Fai;Qu, Yibo;Zhou, Libing
轴突切断诱导的突触剥离调节受损运动神经元的存活和轴突再生。Celsr2被认为在发育过程中介导了相邻细胞之间的亲性相互作用，但它在突触剥离中的作用尚不清楚。在臂丛神经撕脱伤模型中，Celsr2基因敲除改善了功能恢复、运动神经元存活和轴突再生。Celsr2LacZ小鼠的脊髓运动神经元、兴奋性和抑制性中间神经元、星形胶质细胞和部分少突胶质细胞表达Celsr2。双重免疫染色显示，损伤后运动神经元上抑制性和兴奋性小泡的覆盖率明显减少，而−/−突变体中保留的抑制性小泡明显多于对照小鼠。在超微结构中，Celsr2−/−突变体损伤运动神经元上抑制F-Bouton的密度高于对照。在星形胶质细胞或少突胶质细胞中条件性敲除Celsr2显示出与对照组相似的轴突切断引起的突触撤退。损伤脊髓样本的RNAseq鉴定出12个MHC I分子，这些分子在Celsr2−/−和对照组小鼠之间发生了显著变化。损伤后，损伤运动神经元周围MHC I的表达增加，尤其是在Celsr2−/−突变体中表达增加。总之，Celsr2基因敲除增强了MHC I信号，自主地减轻了突触剥离细胞的抑制作用，并有助于运动神经元的存活和再生，Celsr2是神经修复的潜在靶点。网上版载有补充材料，可在10.1007/s12035-022-03198-3查阅。
Axotomy-induced synaptic stripping modulates survival and axon regeneration of injured motoneurons. Celsr2 is supposed to mediate homophilic interactions of neighboring cells during development, and its role in synaptic stripping remains unknow. In a model of brachial plexus avulsion, Celsr2 knockout improved functional recovery, motoneuron survival, and axon regeneration. Celsr2 was indicated to express in spinal motoneurons, excitatory and inhibitory interneurons, astrocytes, and a subset of oligodendrocytes using Celsr2LacZ mice. Double immunostaining showed that the coverage of inhibitory and excitatory vesicles on injured motoneurons were remarkably reduced after injury, whereas more inhibitory vesicles were maintained in Celsr2−/− mutants than control mice. In the ultrastructure, the density of inhibitory F-boutons on injured motoneurons was higher in Celsr2−/− mutants than controls. Conditional knockout of Celsr2 in astrocytes or oligodendrocytes showed the similar axotomy-induced synaptic withdrawal to the control. RNAseq of injured spinal samples identified 12 MHC I molecules with significant changes between Celsr2−/− and control mice. After injury, expression of MHC I surrounding injured motoneurons was increased, particularly high in Celsr2−/− mutants. In conclusion, Celsr2 knockout enhances MHC I signaling, alleviates inhibitory synaptic stripping cell-autonomously, and contributes to motoneuron survival and regeneration, and Celsr2 is a potential target for neural repair. The online version contains supplementary material available at 10.1007/s12035-022-03198-3.
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影响因子：
3.5
作者：
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通讯作者：
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