LXR的无效或激活改变了小脑中的髓鞘结构和髓鞘基因表达。（a）小脑WT和LXR DKO电子显微照片的低放大率。（秤条，2μm。）（b）代表性轴突的高倍率电子显微照片及其髓层。（尺度棒，50nm。）（c）髓鞘厚度估计由G比估计（平均±SEM，每组3只动物; ** P <0.01通过T测试）。（d）WT和LXR DKO小脑RNA的定量RT-PCR，其引物识别PLP，MBP或ABCA1（阳性对照）与GAPDH（甘氨醛3-磷酸脱氢酶）标准化（每组N = 5只动物的平均值±SEM; ** P <0.01和*** P <0.001通过T检验）。（e）来自WT和LXR DKO小脑蛋白的Western印迹使用抗PLP和抗MBP抗体与β-肌动蛋白标准化（每组N = 4只动物的平均值±SEM; ** P <0.01和*** P <0.001通过T测试）。图片代表一个典型的实验。（f）来自WT小鼠的小脑RNA的定量RT-PCR，用致血压喂食PLP，MBP或ABCA1的引物（每组N = 5只动物的平均±SEM; * P <0.05和** P <0.01对T检验）。（g）使用与β-肌动蛋白的抗PLP和抗MBP抗体（每组N = 5只动物的平均±SEM归一化的抗PLP和抗MBP抗体的WT强烈喂食蛋白质蛋白质的蛋白质印迹。 (H) Cerebellar RNA from LXR dKO force-fed with TO9 as analyzed in F. Credit: Meffre, D et al. (2015) Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum.Proc Natl academy Sci美国112：24 7587-7592。
LXR活化加速有机型小脑培养物中的重新髓鞘。用EtOH，TO 9或25-OH处理对照（载体）和溶血性脱髓鞘切片。After (A) double immunostaining for MBP and CaBP and confocal acquisition, (B) axon number and (C) percentage of myelinated fibers were quantified (***P < 0.001 by ANOVA and Tukey’s post hoc test; n = 18 animals per group). (Scale bar, 20 μm.) (D and E) Quantitative RT-PCR with primers recognizing PLP, MBP, and ABCA1 normalized using 26S (mean ± SEM of at least three independent experiments performed in duplicate; *P < 0.05 by t test). (F) Western blots for PLP and MBP normalized with β-actin and reproduced at least in three independent experiments (mean ± SEM; *P < 0.05 and **P < 0.01 by t test). (G) Control (vehicle) and lysolecithin-demyelinated organotypic slices treated with EtOH, TO9, or 25-OH. After immunostaining for Nkx2.2, numbers of immature oligodendrocytes were quantified with ImageJ (n = 12 animals per group; *P < 0.05, **P < 0.01, and ***P < 0.001 by t test). Representative micrographs are shown. (Scale bar, 50 μm.) (H) Control (vehicle) and demyelinated organotypic slices treated for 3 DIV with EtOH, TO9, or 25-OH and doubled immunostained for Caspr and MAG. A 5× magnification of a single Caspr cluster (pointed by the open arrowhead) is presented in each picture. (I) Number of Caspr clusters, (J) internode lengths, and (K) node lengths measured using ImageJ (means ± SEM; *P < 0.05, **P < 0.01, and ***P < 0.001 by t test). Credit: Meffre, D et al. (2015) Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum.Proc Natl academy Sci美国112：24 7587-7592。
LXRs的存在对于氧化甾醇诱导的体外再髓再生至关重要。我们检测了LXRs在TO9和25-OH再生作用中的意义。LXR dKO小脑切片采用与WT相同的方法脱髓鞘。(A) P10 LXR dKO小鼠小脑的器官型切片脱髓鞘，并与WT一样，在图4A中采用EtOH、TO9或25-OH处理。对MBP和CaBP进行双重免疫染色后，用Zeiss LSM 510共焦获得图像。(比例尺，20 μm。)溶血卵磷脂治疗导致髓鞘网络的明显混乱。(B)轴突数量和(C)髓鞘纤维百分比用ImageJ定量。***P < 0.001，采用单因素方差分析，然后采用Tukey事后检验。每组18只动物。TO9和25-OH对轴突数量和有髓纤维百分比无影响。 (D) Demyelinated organotypic slices were treated for 3 DIV with EtOH, TO9, or 25-OH (10 μM) and doubled immunostained for Caspr and MAG. No Caspr clustering was detectable after TO9 or 25-OH treatment, suggesting that the remyelination process was impaired in organotypic slices invalidated for LXRs. Credit: Meffre, D et al. (2015) Liver X receptors alpha and beta promote myelination and remyelination in the cerebellum.Proc Natl academy Sci美国112：24 7587-7592。
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