PDF(Pubmed)
Abstract：
Demyelination is generated in several nervous system illnesses. Developing strategies for effective clinical treatments requires the discovery of promyelinating drugs. Increased GABAergic signaling through γ-aminobutyric acid type A receptor (GABAAR) activation in oligodendrocytes has been proposed as a promyelinating condition. GABAAR expressed in oligodendroglia is strongly potentiated by n-butyl-β-carboline-3-carboxylate (β-CCB) compared to that in neurons. Here, mice were subjected to 0.3% cuprizone (CPZ) added in the food to induce central nervous system demyelination, a well-known model for multiple sclerosis. Then β-CCB (1 mg/Kg) was systemically administered to analyze the remyelination status in white and gray matter areas. Myelin content was evaluated using Black-Gold II (BGII) staining, immunofluorescence (IF), and magnetic resonance imaging (MRI). Evidence indicates that β-CCB treatment of CPZ-demyelinated animals promoted remyelination in several white matter structures, such as the fimbria, corpus callosum, internal capsule, and cerebellar peduncles. Moreover, using IF, it was observed that CPZ intake induced an increase in NG2+ and a decrease in CC1+ cell populations, alterations that were importantly retrieved by β-CCB treatment. Thus, the promyelinating character of β-CCB was confirmed in a generalized demyelination model, strengthening the idea that it has clinical potential as a therapeutic drug.
摘要：
脱髓鞘在几种神经系统疾病中产生。制定有效的临床治疗策略需要发现促髓鞘化药物。已提出通过少突胶质细胞中的γ-氨基丁酸A型受体（GABAAR）激活增加的GABA能信号传导作为早髓鞘化条件。与神经元相比，在少突胶质细胞中表达的GABAAR被正丁基-β-咔啉-3-羧酸酯（β-CCB）强烈增强。这里,小鼠在食物中加入0.3%的铜氮酮（CPZ）诱导中枢神经系统脱髓鞘，一种众所周知的多发性硬化症模型。然后全身施用β-CCB(lmg/Kg)以分析白质和灰质区域的髓鞘再生状态。使用黑金II（BGII）染色评估髓磷脂含量，免疫荧光（IF），磁共振成像（MRI）。有证据表明，CPZ脱髓鞘动物的β-CCB治疗促进了几种白质结构的髓鞘再生，比如菌毛，call体,内囊,还有小脑梗.此外，使用IF，观察到CPZ摄入诱导NG2+增加和CC1+细胞群减少，通过β-CCB治疗获得的重要改变。因此，在广泛性脱髓鞘模型中证实了β-CCB的早幼髓鞘化特征，加强了它作为治疗药物具有临床潜力的想法。
