Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey; UNAM - National Nanotechnology Research Center and Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey; Department of Molecular Biology and Genetics Zebrafish Facility, Bilkent University, Ankara, Turkey.
Interdisciplinary Graduate Program in Neuroscience, Aysel Sabuncu Brain Research Center, Bilkent University, Ankara, Turkey; UNAM - National Nanotechnology Research Center and Institute of Materials Science and Nanotechnology, Bilkent University, Ankara, Turkey; Department of Molecular Biology and Genetics Zebrafish Facility, Bilkent University, Ankara, Turkey; Stem Cell Research and Application Center, Hacettepe University, Ankara, Turkey.
Neurobiol Aging. 2020 Oct;94:164-175. doi: 10.1016/j.neurobiolaging.2020.04.017. Epub 2020 May 12.
Brain aging is a complex process, which involves multiple pathways including various components from cellular to molecular. This study aimed to investigate the gene expression changes in zebrafish brains through young-adult to adult, and adult to old age. RNA sequencing was performed on isolated neuronal cells from zebrafish brains. The cells were enriched in progenitor cell markers, which are known to diminish throughout the aging process. We found 176 statistically significant, differentially expressed genes among the groups, and identified a group of genes based on gene ontology descriptions, which were classified as cell adhesion molecules. The relevance of these genes was further tested in another set of zebrafish brains, human healthy, and Alzheimer's disease brain samples, as well as in Allen Brain Atlas data. We observed that the expression change of 2 genes, GJC2 and ALCAM, during the aging process was consistent in all experimental sets. Our findings provide a new set of markers for healthy brain aging and suggest new targets for therapeutic approaches to neurodegenerative diseases.
大脑衰老过程复杂，涉及多个途径，包括从细胞到分子的各种成分。本研究旨在通过幼鱼到成鱼、成鱼到老年鱼，研究斑马鱼大脑中的基因表达变化。对从斑马鱼大脑中分离的神经元细胞进行了 RNA 测序。这些细胞富含祖细胞标志物，已知这些标志物在衰老过程中会减少。我们在这些组之间发现了 176 个具有统计学意义的差异表达基因，并根据基因本体描述确定了一组基因，这些基因被归类为细胞粘附分子。这些基因的相关性在另一组斑马鱼大脑、人类健康和阿尔茨海默病大脑样本以及艾伦大脑图谱数据中进行了进一步测试。我们观察到，在所有实验组中，GJC2 和 ALCAM 这 2 个基因在衰老过程中的表达变化是一致的。我们的研究结果为健康大脑衰老提供了一组新的标志物，并为神经退行性疾病的治疗方法提供了新的靶点。
