Dicer Deletion in Astrocytes Inhibits Oligodendroglial Differentiation and Myelination.
Dicer Deletion in Astrocytes Inhibits Oligodendroglial Differentiation and Myelination.
复制标题
DOI：
10.1007/s12264-021-00705-9
复制
发表时间：
2021-08
影响因子：
5.6
通讯作者：
Xiao L
中科院分区：
文献类型：
--
作者：
Liu K;Yu B;Chen JF;Li RX;Chen L;Ren SY;Wang F;Mei F;Xiao L
越来越多的证据表明星形胶质细胞参与调节少突胶质细胞的髓鞘形成，但其潜在机制仍不清楚。为了了解星形胶质细胞中的microrna是否在调节发育和成年中枢神经系统的少突胶质分化和髓鞘形成中起作用，我们产生了可诱导的星形胶质细胞特异性Dicer条件敲除小鼠（hgap - creert; Dicer fl/fl）。通过使用报告小鼠系（mT/mG），我们证实了hgmap - creert在出生后第3天（P3）至第7天（P7）接受他莫昔芬治疗后，在发育中的中枢神经系统中驱动有效的星形细胞特异性重组。星形胶质细胞中Dicer的缺失导致Dicer cKO小鼠在P10和P14时中枢神经系统少突胶质细胞分化和髓鞘形成受到抑制，且未改变神经元和轴突的密度，表明星形胶质细胞中的Dicer是少突胶质细胞髓鞘形成所必需的。因此，P3星形胶质细胞中的Dicer缺失导致9周龄时空间记忆和运动协调能力受损。为了了解星形胶质细胞中的Dicer是否也是脱髓鞘再生所必需的，我们在3月龄小鼠中诱导Dicer缺失，然后在胼胝体中注射溶卵磷脂来诱导脱髓鞘。星形胶质细胞Dicer的缺失阻断了诱导脱髓鞘后14天胼胝体的再髓鞘形成。总之，我们的研究结果表明星形胶质细胞中的Dicer是发育和成人中枢神经系统中少突胶质细胞髓鞘形成所必需的。
Increasing evidence has shown that astrocytes are implicated in regulating oligodendrocyte myelination, but the underlying mechanisms remain largely unknown. To understand whether microRNAs in astrocytes function in regulating oligodendroglial differentiation and myelination in the developing and adult CNS, we generated inducible astrocyte-specific Dicer conditional knockout mice (hGFAP-CreERT; Dicer fl/fl). By using a reporter mouse line (mT/mG), we confirmed that hGFAP-CreERT drives an efficient and astrocyte-specific recombination in the developing CNS, upon tamoxifen treatment from postnatal day 3 (P3) to P7. The Dicer deletion in astrocytes resulted in inhibited oligodendroglial differentiation and myelination in the developing CNS of Dicer cKO mice at P10 and P14, and did not alter the densities of neurons or axons, indicating that Dicer in astrocytes is required for oligodendrocyte myelination. Consequently, the Dicer deletion in astrocytes at P3 resulted in impaired spatial memory and motor coordination at the age of 9 weeks. To understand whether Dicer in astrocytes is also required for remyelination, we induced Dicer deletion in 3-month-old mice and then injected lysolecithin into the corpus callosum to induce demyelination. The Dicer deletion in astrocytes blocked remyelination in the corpus callosum 14 days after induced demyelination. Together, our results indicate that Dicer in astrocytes is required for oligodendroglia myelination in both the developing and adult CNS.
登录
查看更多内容
影响因子：
4
作者：
Niu, Jianqin;Li, Tao;Xiao, Lan
通讯作者：
Xiao, Lan
影响因子：
5.3
作者：
Rash, JE;Yasumura, T;Nagy, JI
通讯作者：
Nagy, JI
成熟髓鞘神经胶质细胞中切丁酶的缺失会导致成年小鼠进行性轴突变性，但不会导致明显的脱髓鞘
影响因子：
6.2
作者：
Li, Tao;Wang, Jingjing;Xiao, Lan
通讯作者：
Xiao, Lan
影响因子：
6.2
作者：
Padovani-Claudio, Dolly A.;Liu, Liping;Miller, Robert H.
通讯作者：
Miller, Robert H.
星形胶质细胞中连接蛋白 43 缺失通过调节局部炎症促进中枢神经系统髓鞘再生
影响因子：
6.2
作者：
Li, Tao;Niu, Jianqin;Xiao, Lan
通讯作者：
Xiao, Lan