Glutamate delta-1 receptor regulates oligodendrocyte progenitor cell differentiation and myelination in normal and demyelinating conditions.
Glutamate delta-1 receptor regulates oligodendrocyte progenitor cell differentiation and myelination in normal and demyelinating conditions.
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DOI：
10.1371/journal.pone.0294583
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发表时间：
2023
期刊：
影响因子：
3.7
通讯作者：
中科院分区：
文献类型：
--
作者：
在这项研究中，我们调查的作用，谷氨酸δ 1受体（GluD 1）在少突胶质细胞祖细胞（OPC）介导的髓鞘形成过程中的基础（发展）和病理生理（铜蛋白诱导的脱髓鞘）条件。最初，我们试图确定GluD 1在OPCs中的表达模式，发现GluD 1斑点与运动皮质和背侧纹状体中的神经元-胶质细胞抗原2（NG 2，OPC标记物）显著共定位。重要的是，我们发现GluD 1的消融导致P40时胼胝体和运动皮质中髓鞘相关糖蛋白（MAG+）细胞数量增加，而不影响NG 2 + OPC的数量，这表明GluD 1的缺失选择性地促进OPC分化而不是增殖。此外，GluD 1的缺失增强了胼胝体和运动皮层的髓鞘形成，如P40时髓鞘碱性蛋白（MBP）染色增加所示，表明GluD 1可能在关键窗口期的髓鞘形成的发育调节中发挥重要作用。与此相反，在铜蛋白腙诱导的脱髓鞘，我们观察到减少MBP染色的GluD 1基因敲除小鼠胼胝体。此外，cuprizone喂养的GluD 1 KO小鼠表现出更强大的运动缺陷。总的来说，我们的研究结果表明，GluD 1在正常和脱髓鞘条件下的OPC调节和髓鞘形成中起着关键作用。
In this study, we investigated the role of glutamate delta 1 receptor (GluD1) in oligodendrocyte progenitor cell (OPC)-mediated myelination during basal (development) and pathophysiological (cuprizone-induced demyelination) conditions. Initially, we sought to determine the expression pattern of GluD1 in OPCs and found a significant colocalization of GluD1 puncta with neuron-glial antigen 2 (NG2, OPC marker) in the motor cortex and dorsal striatum. Importantly, we found that the ablation of GluD1 led to an increase in the number of myelin-associated glycoprotein (MAG+) cells in the corpus callosum and motor cortex at P40 without affecting the number of NG2+ OPCs, suggesting that GluD1 loss selectively facilitates OPC differentiation rather than proliferation. Further, deletion of GluD1 enhanced myelination in the corpus callosum and motor cortex, as indicated by increased myelin basic protein (MBP) staining at P40, suggesting that GluD1 may play an essential role in the developmental regulation of myelination during the critical window period. In contrast, in cuprizone-induced demyelination, we observed reduced MBP staining in the corpus callosum of GluD1 KO mice. Furthermore, cuprizone-fed GluD1 KO mice showed more robust motor deficits. Collectively, our results demonstrate that GluD1 plays a critical role in OPC regulation and myelination in normal and demyelinating conditions.
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影响因子：
12.7
作者：
Bradl M;Lassmann H
通讯作者：
Lassmann H
影响因子：
3.1
作者：
Goldberg, Johannes;Clarner, Tim;Kipp, Markus
通讯作者：
Kipp, Markus
影响因子：
64.8
作者：
Bergles, DE;Roberts, JDB;Jahr, CE
通讯作者：
Jahr, CE
影响因子：
9.3
作者：
Gawande, Dinesh Y.;Narasimhan, Kishore Kumar S.;Bhatt, Jay M.;Pavuluri, Ratnamala;Kesherwani, Varun;Suryavanshi, Pratyush S.;Shelkar, Gajanan P.;Dravid, Shashank M.
通讯作者：
Dravid, Shashank M.
影响因子：
3.3
作者：
Acs, P.;Selak, M. A.;Kalman, B.
通讯作者：
Kalman, B.