GluA2 overexpression in oligodendrocyte progenitors promotes postinjury oligodendrocyte regeneration.
GluA2 overexpression in oligodendrocyte progenitors promotes postinjury oligodendrocyte regeneration.
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DOI：
10.1016/j.celrep.2021.109147
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发表时间：
2021-05-18
期刊：
影响因子：
8.8
通讯作者：
Kang SH
中科院分区：
文献类型：
--
作者：
Khawaja RR;Agarwal A;Fukaya M;Jeong HK;Gross S;Gonzalez-Fernandez E;Soboloff J;Bergles DE;Kang SH
少突胶质前体细胞是中枢神经系统损伤后发育中髓鞘形成和少突胶质细胞再生所必需的。这些前体细胞表达钙通透性AMPA受体(AMPAR)，并与整个中枢神经系统的神经元形成直接突触，但这种信号转导的作用尚不清楚。为了能够选择性地改变少突胶质细胞中AMPAR的性质，我们产生了允许细胞特异性在体内过表达EGFP-GluA2的小鼠。在健康条件下，OPC特异性GluA2的过度表达显著促进了它们的增殖，并呈年龄依赖性，但不改变它们向少突胶质细胞的分化率。相反，在新生儿或成人脑损伤脱髓鞘后，较高的GluA2水平促进OPC增殖和少突胶质细胞再生，但不能阻止损伤诱导的初始细胞丢失。这些发现表明，AMPAR GluA2含量调节成年OPC的增殖和再生行为，可能是更好的髓鞘修复的靶点。Khawaja等人。结果表明，在脱髓鞘脑损伤中，少突胶质前体细胞GluA2的表达增加，使AMPA受体钙离子不通透，但不改变少突胶质细胞的生成，但促进少突胶质细胞的增殖和再生，提示抑制少突胶质前体细胞的AMPA受体钙信号转导有助于促进髓鞘修复。
Oligodendrocyte precursor cells (OPCs) are essential for developmental myelination and oligodendrocyte regeneration after CNS injury. These progenitors express calcium-permeable AMPA receptors (AMPARs) and form direct synapses with neurons throughout the CNS, but the roles of this signaling are unclear. To enable selective alteration of the properties of AMPARs in oligodendroglia, we generate mice that allow cell-specific overexpression of EGFP-GluA2 in vivo. In healthy conditions, OPC-specific GluA2 overexpression significantly increase their proliferation in an age-dependent manner but did not alter their rate of differentiation into oligodendrocytes. In contrast, after demyelinating brain injury in neonates or adults, higher GluA2 levels promote both OPC proliferation and oligodendrocyte regeneration, but do not prevent injury-induced initial cell loss. These findings indicate that AMPAR GluA2 content regulates the proliferative and regenerative behavior of adult OPCs, serving as a putative target for better myelin repair. Khawaja et al. show that increasing expression of GluA2 in oligodendrocyte precursor cells (OPCs), which renders AMPA receptors calcium impermeable, did not alter oligodendrocyte generation, but promoted OPC proliferation and oligodendrocyte regeneration in demyelinating brain injury, suggesting that suppressing AMPA receptor calcium signaling in OPCs could help promote myelin repair.
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影响因子：
16.6
作者：
Berret E;Barron T;Xu J;Debner E;Kim EJ;Kim JH
通讯作者：
Kim JH
DOI：
10.1523/jneurosci.6000-09.2010
发表时间：
2010-03-10
期刊：
The Journal of neuroscience : the official journal of the Society for Neuroscience
影响因子：
--
作者：
De Biase LM;Nishiyama A;Bergles DE
通讯作者：
Bergles DE
影响因子：
16.2
作者：
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通讯作者：
Bergles, Dwight E.
影响因子：
64.8
作者：
Bergles, DE;Roberts, JDB;Jahr, CE
通讯作者：
Jahr, CE
影响因子：
7.7
作者：
Kougioumtzidou, Eleni;Shimizu, Takahiro;Richardson, William D.
通讯作者：
Richardson, William D.