小脑颗粒细胞培养作为抗抑郁药物诱导神经发生的体外模型。

M Zusso, P Debetto, D Guidolin, P Giusti
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引用次数: 15

摘要

临床前和临床证据均表明,抗抑郁药物上调海马细胞增殖和神经发生。此外,最近发表的直接证据表明,海马体新生细胞增殖是抗抑郁作用所必需的。在这个框架内,我们使用大鼠小脑颗粒细胞(CGC)的原代培养物作为中枢神经系统(CNS)的体外模型,研究选择性5 -羟色胺再摄取抑制剂(SSRIs)慢性治疗后,是否也可以在小脑中引发神经源性反应。此外,我们分析了CGC中神经前体细胞的存在,可能对增殖和分化刺激有反应。我们发现,通过[3H]-胸腺嘧啶掺入检测,1微米氟西汀可增加细胞增殖。神经细胞特异性标记物的CGC免疫细胞化学分析显示颗粒神经元、胶质细胞和我们命名为“圆细胞”的细胞成分的存在。由于只有圆形细胞表现出增殖能力,正如5-溴-2'-脱氧尿苷(BrdU)标记所显示的那样,它们被进一步表征。为此,在免疫细胞化学分析之前,将圆形细胞分离并在含碱性成纤维细胞生长因子(bFGF)的无血清培养基中培养。我们发现圆形细胞对神经胶质、神经元和少突胶质细胞标记物没有免疫反应,而对几种未成熟的神经元标记物有免疫反应。因此,圆形细胞可以被诱导分化为星形胶质细胞、神经元和少突胶质细胞,要么通过提取有丝分裂原bFGF,要么通过将它们暴露于氟西汀。这些发现表明,CGC中的圆形细胞具有神经前体的特征和潜力,能够在药理学模拟下在成熟的神经细胞中分化。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Cerebellar granular cell cultures as an in vitro model for antidepressant drug-induced neurogenesis.

Both preclinical and clinical evidence suggested that antidepressant drugs upregulate hippocampal cell proliferation and neurogenesis. In addition, direct evidence was recently published that hippocampal de novo cell proliferation is necessary for antidepressant action. Within this frame, we used primary cultures of rat cerebellar granule cells (CGC) as an in vitro model of central nervous system (CNS) to investigate whether a neurogenic response could be elicited also in the cerebellum, upon chronic treatment with selective serotonin reuptake inhibitors (SSRIs). Furthermore, we assayed the presence of neural precursor cells in CGC, possibly responsive to proliferation and differentiation stimuli. We found that 1 microM fluoxetine increased cell proliferation, as assayed by [3H]-thymidine incorporation. CGC immunocytochemical analysis with neural cell-specific markers revealed the presence of granule neurons, glial cells, and a cell component that we named "round cells." Because only round cells displayed proliferation ability, as revealed by 5-bromo-2'-deoxyuridine (BrdU) labeling, they were further characterized. For this purpose, round cells were isolated and expanded by culturing in a serum-free medium, containing basic fibroblast growth factor (bFGF), before immunocytochemical analysis. We found that round cells were not immunoreactive for glial, neuronal, and oligodendrocyte markers, whereas they were immunoreactive for several immature neuronal markers. Accordingly, round cells could be induced to differentiate into astrocytes, neurons, and oligodendrocytes, either by withdrawing the mitogen bFGF or by exposing them to fluoxetine. These findings suggest that round cells in CGC possess the features and potentials of neural precursors, able to differentiate in mature neural cells upon a pharmacological simulum.

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