Department of Physiology, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran.
Department of Stem Cells and Developmental Biology at Cell Science Research Center, Royan Institute for Stem Cell Biology and Technology, ACECR, Tehran, Iran.
Biomed Pharmacother. 2017 Sep;93:1074-1082. doi: 10.1016/j.biopha.2017.07.043. Epub 2017 Jul 18.
The effects of Wnt signaling modifiers on cell proliferation, seem to be cell specific. Enhancing the proliferation of subventricular zone (SVZ) progenitors has been in the focus of research in recent years. Here we investigate the effect of CHIR99021, a Glycogen Synthase Kinase 3 (GSk-3) inhibitor, on SVZ progenitor's proliferation both in vivo and in vitro. Neural stem cells were extracted from the adult C57bl/6 by mincing and trypsin treatment followed by culturing in specific medium. Sphere cells formed within about 7-10days and were characterized by immunostaining. Number of spheres and their size was assessed following exposure to different concentration of CHIR99021 or vehicle. For in vivo studies, animals received intracerebroventricular (i.c.v.) injection of CHIR99021 or vehicle for four days. A subgroup of animals, after 4days treatment with CHIR99021 received intranasal kainic acid to induce local neurodegeneration in CA3 area of hippocampus. Inhibition of GSk-3 by CHIR99021 increased neural progenitor proliferation and the effect of CHIR99021 was long lasting so that the treated cells showed higher proliferation even after CHIR99021 removal. In vivo administration of CHIR99021 increased the number of neural progenitors at the rims of lateral ventricles especially when the treatment was followed by kainic acid administration which induces neural insult. Results showed that direct administration of CHIR99021 into the culture medium or animal brain increased the number of SVZ progenitors, especially when a neural insult was induced in the hippocampus.
Wnt 信号调节剂对细胞增殖的影响似乎具有细胞特异性。近年来，人们一直关注增强侧脑室（SVZ）祖细胞的增殖。在这里，我们研究了 Glycogen Synthase Kinase 3（GSk-3）抑制剂 CHIR99021 对 SVZ 祖细胞在体内和体外增殖的影响。我们通过切碎和胰蛋白酶处理从成年 C57bl/6 中提取神经干细胞，然后在特定培养基中培养。大约 7-10 天后，球体细胞形成，并通过免疫染色进行特征鉴定。在暴露于不同浓度的 CHIR99021 或载体后，评估球体的数量及其大小。对于体内研究，动物接受侧脑室内（i.c.v.）注射 CHIR99021 或载体四天。在 CHIR99021 治疗 4 天后，动物亚组接受鼻内海人酸注射以诱导海马 CA3 区局部神经退行性变。CHIR99021 通过抑制 GSk-3 增加神经祖细胞的增殖，并且 CHIR99021 的作用是持久的，以至于即使在去除 CHIR99021 后，处理过的细胞仍显示出更高的增殖。CHIR99021 的体内给药增加了侧脑室边缘的神经祖细胞数量，尤其是当治疗后进行海人酸给药诱导神经损伤时。结果表明，CHIR99021 直接给药到培养基或动物大脑中会增加 SVZ 祖细胞的数量，尤其是在海马中诱导神经损伤时。
