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Abstract：
Leucine-rich repeat kinase-2 (LRRK2), a gene mutated in familial and sporadic Parkinson\'s disease (PD), controls multiple cellular processes important for GLIA physiology. Interestingly, emerging studies report that LRRK2 is highly expressed in oligodendrocyte precursor cells (OPCs) compared to the pathophysiology of other brain cells and oligodendrocytes (OLs) in PD. Altogether, these observations suggest crucial function(s) of LRRK2 in OPCs/Ols, which would be interesting to explore. In this study, we investigated the role of LRRK2 in OLs. We showed that LRRK2 knock-out (KO) OPC cultures displayed defects in the transition of OPCs into OLs, suggesting a role of LRRK2 in OL differentiation. Consistently, we found an alteration of myelin basic protein (MBP) striosomes in LRRK2 KO mouse brains and reduced levels of oligodendrocyte transcription factor 2 (Olig2) and Mbp in olig2:EGFP and mbp:RFP transgenic zebrafish embryos injected with lrrk2 morpholino (MO). Moreover, lrrk2 knock-down zebrafish exhibited a lower amount of nerve growth factor (Ngf) compared to control embryos, which represents a potent regulator of oligodendrogenesis and myelination. Overall, our findings indicate that LRRK2 controls OL differentiation, affecting the number of mature OLs.
摘要：
富含亮氨酸的重复激酶-2（LRRK2），在家族性和散发性帕金森病（PD）中突变的基因，控制对GLIA生理学重要的多个细胞过程。有趣的是,新兴研究报告，与PD中其他脑细胞和少突胶质细胞（OL）的病理生理学相比，LRRK2在少突胶质细胞前体细胞（OPC）中高表达。总之,这些观察表明LRRK2在OPC/Ols中的关键功能，这将是有趣的探索。在这项研究中,我们研究了LRRK2在OLs中的作用。我们表明，LRRK2敲除（KO）OPC培养物在OPC向OLs的转变中表现出缺陷，提示LRRK2在OL分化中的作用。始终如一，我们发现LRRK2KO小鼠大脑中髓鞘碱性蛋白(MBP)的纹状体发生改变,在注射了lrrk2吗啉代(MO)的olig2:EGFP和mbp:RFP转基因斑马鱼胚胎中,少突胶质细胞转录因子2(Olig2)和Mbp水平降低.此外，与对照胚胎相比，lrrk2敲低斑马鱼表现出更低的神经生长因子（Ngf）含量，它代表了少突形成和髓鞘形成的有效调节剂。总的来说,我们的发现表明LRRK2控制OL分化，影响成熟OL的数量。
