Pediatric Center, Semmelweis University, Budapest, Hungary; Vascular Cognitive Impairment, Neurodegeneration and Healthy Brain Aging Program, Department of Neurosurgery, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA; Oklahoma Center for Geroscience and Healthy Brain Aging, University of Oklahoma Health Sciences Center, Oklahoma City, OK, USA.
Department of Cell Biology and Molecular Medicine, University of Szeged, Szeged, Hungary; Department of Computational Sciences, Wigner Research Centre for Physics, Budapest, Hungary; Department of Anatomy, Histology and Embryology, Semmelweis University, Budapest, Hungary.
Brain Res. 2023 Nov 1;1818:148517. doi: 10.1016/j.brainres.2023.148517. Epub 2023 Aug 7.
Microglia cells, the immune cells residing in the brain, express immune regulatory molecules that have a central role in the manifestation of age-related brain characteristics. Our hypothesis suggests that galectin-1, an anti-inflammatory member of the beta-galactoside-binding lectin family, regulates microglia and neuroinflammation in the aging brain. Through our in-silico analysis, we discovered a subcluster of microglia in the aged mouse brain that exhibited increased expression of galectin-1 mRNA. In our Western blotting experiments, we observed a decrease in galectin-1 protein content in our rat primary cortical cultures over time. Additionally, we found that the presence of lipopolysaccharide, an immune activator, significantly increased the expression of galectin-1 protein in microglial cells. Utilizing flow cytometry, we determined that a portion of the galectin-1 protein was localized on the surface of the microglial cells. As cultivation time increased, we observed a decrease in the expression of activation-coupled molecules in microglial cells, indicating cellular exhaustion. In our mixed rat primary cortical cell cultures, we noted a transition of amoeboid microglial cells labeled with OX42(CD11b/c) to a ramified, branched phenotype during extended cultivation, accompanied by a complete disappearance of galectin-1 expression. By analyzing the transcriptome of a distinct microglial subpopulation in an animal model of aging, we established a correlation between chronological aging and galectin-1 expression. Furthermore, our in vitro study demonstrated that galectin-1 expression is associated with the functional activation state of microglial cells exhibiting specific amoeboid morphological characteristics. Based on our findings, we identify galectin-1 as a marker for microglia activation in the context of aging.
小胶质细胞是驻留在大脑中的免疫细胞，表达免疫调节分子，这些分子在表现与年龄相关的大脑特征方面起着核心作用。我们的假设表明，半乳糖凝集素-1 是半乳糖结合凝集素家族中的一种抗炎成员，调节衰老大脑中的小胶质细胞和神经炎症。通过我们的计算机分析，我们发现衰老小鼠大脑中的一个小胶质细胞亚群表现出 galectin-1 mRNA 的表达增加。在我们的 Western blot 实验中，我们观察到大鼠原代皮质培养物中的 galectin-1 蛋白含量随时间的推移而减少。此外，我们发现免疫激活剂脂多糖的存在显著增加了小胶质细胞中 galectin-1 蛋白的表达。利用流式细胞术，我们确定一部分 galectin-1 蛋白定位于小胶质细胞的表面。随着培养时间的增加，我们观察到小胶质细胞中激活偶联分子的表达减少，表明细胞衰竭。在我们的混合大鼠原代皮质细胞培养物中，我们注意到 OX42（CD11b/c）标记的阿米巴样小胶质细胞在延长培养过程中向分支状、分支状表型转变，同时 galectin-1 表达完全消失。通过分析衰老动物模型中一个特定小胶质细胞亚群的转录组，我们建立了随时间推移的衰老与 galectin-1 表达之间的相关性。此外，我们的体外研究表明，galectin-1 表达与表现出特定阿米巴样形态特征的小胶质细胞的功能激活状态相关。基于我们的发现，我们将 galectin-1 确定为衰老背景中小胶质细胞激活的标志物。
