Myt1L Promotes Differentiation of Oligodendrocyte Precursor Cells and is Necessary for Remyelination After Lysolecithin-Induced Demyelination / 神经科学通报·英文版

The differentiation and maturation of oligodendrocyte precursor cells (OPCs) is essential for myelination and remyelination in the CNS. The failure of OPCs to achieve terminal differentiation in demyelinating lesions often results in unsuccessful remyelination in a variety of human demyelinating diseases. However, the molecular mechanisms controlling OPC differentiation under pathological conditions remain largely unknown. Myt1L (myelin transcription factor 1-like), mainly expressed in neurons, has been associated with intellectual disability, schizophrenia, and depression. In the present study, we found that Myt1L was expressed in oligodendrocyte lineage cells during myelination and remyelination. The expression level of Myt1L in neuron/glia antigen 2-positive (NG2) OPCs was significantly higher than that in mature CC1 oligodendrocytes. In primary cultured OPCs, overexpression of Myt1L promoted, while knockdown inhibited OPC differentiation. Moreover, Myt1L was potently involved in promoting remyelination after lysolecithin-induced demyelination in vivo. ChIP assays showed that Myt1L bound to the promoter of Olig1 and transcriptionally regulated Olig1 expression. Taken together, our findings demonstrate that Myt1L is an essential regulator of OPC differentiation, thereby supporting Myt1L as a potential therapeutic target for demyelinating diseases.

Olig1 gene expression in brain tissue of newborn rat of periventricular leukomalacia and the relation with remyelination / 中国小儿急救医学

Objective To determine Oligl transcription factor expression in periventricular tissue of day 2 newborn rat of periventricular leukomalacia (PVL) and to explore the relation with remyelination.Methods PVL newborn rat model was successfully established through bilateral common carotid artery ligation,followed by 8% oxygen exposure for 30 min. On day 0,day 7 and day 14 after operation,Oligl expression was examined through in situ hybridization, oligodendrocyte precursor cells and oligodendrocytes were detected via immunohistochemistry method and mRNA levels of MBP, PLP, MAG in control and PVL group were examined with quantitative real-time PCR. Results Oligl positive cells of control group were 115 ± 15/mm2. On day 0 and day 7 after operation,oligl positive cells were 72 ± 20/mm2and 75 ± 12/mm2 ,and there was significant difference as compared with control group (P both ＜ 0. 05), however the oligl positive cells on day 14 after operation(146 ± 1 1/mm2) significantly increased with comparison to control group (P ＜0. 05). Compared to control group, GST-Ⅱ positive oligodendrocytes and O4 positive oligodendroglial progenitor cells of PVL group were significantly decreased on day 0, day 7 after operation (P both ＜ 0. 05), and these cells both increased on day 14 after operation ,however there was no difference as compared with control group (P ＞ 0. 05). Compared to control group, mRNA levels of MBP, PLP, MAG all significantly decreased on day 0,day 7 after operation(P all ＜ 0. 05), and these levels slightly increased on day 14 after operation (P ＞ 0. 05). Conclusion Oligl transcription factor may be essential in the remyelination and repair of myelin in PVL.