Corticosteroids (CSs) are widely used clinically, for example in pediatric respiratory distress syndrome, and immunosuppression to prevent rejection of stem cell transplant populations in neural cell therapy. However, such treatment can be associated with adverse effects such as impaired neurogenesis and myelination, and increased risk of cerebral palsy. There is increasing evidence that CSs can adversely influence key biological properties of neural stem cells (NSCs) but the molecular mechanisms underpinning such effects are largely unknown. This is an important issue to address given the key roles NSCs play during brain development and as transplant cells for regenerative neurology. Here, we describe the use of label-free quantitative proteomics in conjunction with histological analyses to study CS effects on NSCs at the cellular and molecular levels, following treatment with methylprednisolone (MPRED). Immunocytochemical staining showed that both parent NSCs and newly generated daughter cells expressed the glucocorticoid receptor, with nuclear localisation of the receptor induced by MPRED treatment. MPRED markedly decreased NSC proliferation and neuronal differentiation while accelerating the maturation of oligodendrocytes, without concomitant effects on cell viability and apoptosis. Parallel proteomic analysis revealed that MPRED induced downregulation of growth associated protein 43 and matrix metallopeptidase 16 with upregulation of the cytochrome P450 family 51 subfamily A member 1. Our findings support the hypothesis that some neurological deficits associated with CS use may be mediated via effects on NSCs, and highlight putative target mechanisms underpinning such effects.

皮质类固醇（CSs）在临床上被广泛使用，例如用于小儿呼吸窘迫综合征和免疫抑制，以防止神经细胞治疗中干细胞移植人群的排斥反应。但是，这种治疗可能与不良反应有关，例如神经发生和髓鞘受损，以及脑瘫的风险增加。越来越多的证据表明，CS可能会对神经干细胞（NSC）的关键生物学特性产生不利影响，但很大程度上尚不清楚支持这种作用的分子机制。考虑到NSC在大脑发育过程中以及作为再生神经学的移植细胞所发挥的关键作用，这是一个重要的问题。这里，我们描述了使用无标记的定量蛋白质组学结合组织学分析来研究CS在甲基强的松龙（MPRED）处理后在细胞和分子水平对NSC的影响。免疫细胞化学染色显示，亲本NSC和新生成的子代细胞均表达糖皮质激素受体，并通过MPRED处理诱导该受体的核定位。MPRED显着降低NSC增殖和神经元分化，同时加速少突胶质细胞的成熟，而对细胞活力和凋亡无伴随影响。平行蛋白质组学分析显示，MPRED诱导了生长相关蛋白43和基质金属肽酶16的下调，而细胞色素P450家族51亚家族A成员1上调。