Iwata Suguru, Hyugaji Mitsuhiro, Soga Yohei, Morikawa Momo, Sasaki Tetsuya, Takei Yosuke
Department of Anatomy and Neuroscience, Institute of Medicine, University of Tsukuba, 1-1- 1, Tennodai, Tsukuba, Ibaraki, 305-8577, Japan.
College of Biological Sciences, University of Tsukuba, 1-1-1, Tennodai, Tsukuba, Ibaraki, 305- 8572, Japan.
BMC Res Notes. 2025 Jan 30;18(1):44. doi: 10.1186/s13104-024-07078-y.
Reactivity of microglia, the resident cells of the brain, underlies innate immune mechanisms (e.g., injury repair), and disruption of microglial reactivity has been shown to facilitate psychiatric disorder dysfunctions. Although cellular analyses based on cultured microglia have been conducted, the molecular mechanism regulating microglial polarization remains elusive. We established a primary microglia culture that enabled manipulation of the substate of cells. This allowed us to investigate the expression levels of psychiatric disorder-related Kifs messenger RNA (mRNA) in each condition. Kifs encode molecular motor proteins that transport cargo along microtubules, which are thought to dynamically reorganize during a substate change.
As a candidate for a crucial Kifs gene that is associated with microglia polarization, we selected psychiatric disorder-related Kifs including Kif17. We found that the relative amounts of Kif3a, Kif17, and Kif13a mRNA were potentiated in alternatively activated microglia, whereas there were no significant changes in activated microglia. Furthermore, the microglia derived from a mouse line which possesses a mutation inducing truncated KIF17 indicated disrupted morphological phenotype of alternatively activated microglia. These results suggest that the potentiation of specific molecular motor expression is required to maintain the function of alternatively activated microglia.
小胶质细胞作为大脑中的常驻细胞，其反应性是先天性免疫机制（如损伤修复）的基础，并且已表明小胶质细胞反应性的破坏会促进精神疾病功能障碍。尽管已经进行了基于培养的小胶质细胞的细胞分析，但调节小胶质细胞极化的分子机制仍然难以捉摸。我们建立了一种原代小胶质细胞培养方法，能够对细胞的亚状态进行操作。这使我们能够研究每种情况下与精神疾病相关的驱动蛋白家族成员（Kifs）信使核糖核酸（mRNA）的表达水平。Kifs编码沿着微管运输货物的分子运动蛋白，而微管被认为在亚状态变化期间会动态重组。
作为与小胶质细胞极化相关的关键Kifs基因的候选基因，我们选择了包括Kif17在内的与精神疾病相关的Kifs。我们发现，在交替激活的小胶质细胞中，Kif3a、Kif17和Kif13a mRNA的相对量增加，而在激活的小胶质细胞中没有显著变化。此外，来自具有诱导截短型KIF17突变的小鼠品系的小胶质细胞显示交替激活的小胶质细胞的形态表型受到破坏。这些结果表明，特定分子运动蛋白表达的增强是维持交替激活的小胶质细胞功能所必需的。
