Minocycline Directly Enhances the Self-Renewal of Adult Neural Precursor Cells
Minocycline Directly Enhances the Self-Renewal of Adult Neural Precursor Cells
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DOI：
10.1007/s11064-017-2422-6
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发表时间：
2018-01
影响因子：
4.4
通讯作者：
Anri Kuroda;Takahiro Fuchigami;S. Fuke;N. Koyama;K. Ikenaka;S. Hitoshi
中科院分区：
文献类型：
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作者：
Anri Kuroda;Takahiro Fuchigami;S. Fuke;N. Koyama;K. Ikenaka;S. Hitoshi
米诺环素不仅具有抗菌作用，而且具有多种药理作用。作为一种治疗许多神经系统疾病中炎症引起的症状的药物，它引起了相当大的关注，导致了几项临床试验。尽管其中一些作用是通过其抑制小胶质细胞激活的功能来实现的，但尚不清楚米诺环素是否作用于成人大脑中的其他细胞类型。在这项研究中，我们利用了一种克隆形成神经球的实验，在这种实验中，神经干细胞(NSCs)克隆性增殖形成漂浮的克隆，称为神经球。我们发现，米诺环素(在脑脊液中的治疗相关浓度)增强了成年小鼠脑室管膜下区神经干细胞的自我更新能力，并促进其分化为少突胶质细胞。重要的是，这些作用与抑制小胶质细胞激活无关，并且米诺环素(在四环素衍生物中)专门观察到了这些作用。此外，在体内将米诺环素通过渗透性小泵注入侧脑室时，成人脑内NSC群体的大小增加。尽管米诺环素如何改变成年神经干细胞行为的确切分子机制尚不清楚，但我们的数据为米诺环素临床用于治疗神经退行性疾病和脱髓鞘疾病提供了基础。
Minocycline not only has antibacterial action but also produces a variety of pharmacological effects. It has drawn considerable attention as a therapeutic agent for symptoms caused by inflammation in many neurological disorders, leading to several clinical trials. Although some of these effects are mediated through its function of suppressing microglial activation, it is not clear whether minocycline acts on other cell types in the adult brain. In this study, we utilized a colony-forming neurosphere assay, in which neural stem cells (NSCs) clonally proliferate to form floating colonies, called neurospheres. We found that minocycline (at therapeutically relevant concentrations in cerebrospinal fluid) enhances the self-renewal capability of NSCs derived from the subependymal zone of adult mouse brain and facilitates their differentiation into oligodendrocytes. Importantly, these effects were independent of a suppression of microglial activation and were specifically observed with minocycline (among tetracycline derivatives). In addition, the size of the NSC population in the adult brain was increased when minocycline was infused into the lateral ventricle by an osmotic minipump in vivo. While precise molecular mechanisms of how minocycline alters the behavior of adult NSCs remain unknown, our data provide a basis for the clinical use of minocycline to treat neurodegenerative and demyelinating diseases.