Serra-Almeida Catarina, Saraiva Cláudia, Esteves Marta, Ferreira Raquel, Santos Tiago, Cristóvão Ana Clara, Bernardino Liliana
Faculty of Health Sciences, Health Sciences Research Centre (CICS-UBI), University of Beira Interior, Covilhã, Portugal.
NeuroSoV, UBImedical, University of Beira Interior, Covilhã, Portugal.
Front Cell Dev Biol. 2021 Jan 6;8:584220. doi: 10.3389/fcell.2020.584220. eCollection 2020.
C-terminal binding proteins (CtBPs) are transcriptional modulators that can regulate gene expression through the recruitment of a corepressor complex composed of chromatin-modifying enzymes and transcriptional factors. In the brain, CtBPs have been described as regulators of cell proliferation, differentiation, and survival. Nevertheless, the role of CtBPs on postnatal neural stem cells (NSCs) fate is not known yet. Herein, we evaluate the expression and functions of CtBPs in postnatal NSCs from the subventricular zone (SVZ). We found that CtBPs were expressed in immature/progenitor cells, neurons and glial cells in the SVZ niche. Using the CtBPs modulator 4-methylthio 2-oxobutyric acid (MTOB), our results showed that 1 mM of MTOB induced cell death, while 5, 25, and 50 μM increased the number of proliferating neuroblasts, mature neurons, and oligodendrocytes. Interestingly, it also increased the dendritic complexity of immature neurons. Altogether, our results highlight CtBPs putative application for brain regenerative applications.
C 末端结合蛋白（CtBPs）是转录调节因子，可通过募集由染色质修饰酶和转录因子组成的共抑制复合物来调节基因表达。在大脑中，CtBPs 被描述为细胞增殖、分化和存活的调节因子。然而，CtBPs 对出生后神经干细胞（NSCs）命运的作用尚不清楚。在此，我们评估了 CtBPs 在脑室下区（SVZ）出生后神经干细胞中的表达和功能。我们发现 CtBPs 在 SVZ 生态位中的未成熟/祖细胞、神经元和胶质细胞中表达。使用 CtBPs 调节剂 4-甲硫基-2-氧代丁酸（MTOB），我们的结果表明，1 mM 的 MTOB 诱导细胞死亡，而 5、25 和 50 μM 的 MTOB 增加了增殖的神经母细胞、成熟神经元和少突胶质细胞的数量。有趣的是，它还增加了未成熟神经元的树突复杂性。总之，我们的结果突出了 CtBPs 在脑再生应用中的潜在应用价值。
