Alzheimer's Disease Genetics Laboratory, School of Biological Sciences, University of Adelaide, North Terrace, Adelaide, SA, 5005, Australia.
Drug Discovery Biology, Monash Institute of Pharmaceutical Sciences, Monash University, Parkville, VIC, 3058, Australia.
Mol Brain. 2021 Jan 25;14(1):22. doi: 10.1186/s13041-021-00734-5.
Previously, we found that brains of adult zebrafish heterozygous for Alzheimer's disease-related mutations in their presenilin 1 gene (psen1, orthologous to human PSEN1) show greater basal expression levels of hypoxia responsive genes relative to their wild type siblings under normoxia, suggesting hypoxic stress. In this study, we investigated whether this might be due to changes in brain vasculature. We generated and compared 3D reconstructions of GFP-labelled blood vessels of the zebrafish forebrain from heterozygous psen1 mutant zebrafish and their wild type siblings. We observed no statistically significant differences in vessel density, surface area, overall mean diameter, overall straightness, or total vessel length normalised to the volume of the telencephalon. Our findings do not support that changes in vascular morphology are responsible for the increased basal expression of hypoxia responsive genes in psen1 heterozygous mutant brains.
此前，我们发现，在 presenilin 1 基因（psen1，与人类 PSEN1 同源）中存在阿尔茨海默病相关突变的杂合子成年斑马鱼大脑，在常氧条件下，相对于其野生型兄弟姐妹，缺氧反应基因的基础表达水平更高，这表明存在缺氧应激。在这项研究中，我们研究了这是否可能是由于大脑血管的变化所致。我们生成并比较了来自杂合子 psen1 突变斑马鱼及其野生型兄弟姐妹的斑马鱼前脑 GFP 标记血管的 3D 重建。我们没有观察到血管密度、表面积、整体平均直径、整体直线度或相对于端脑体积标准化的总血管长度有统计学上的显著差异。我们的发现不支持血管形态的变化是导致 psen1 杂合突变大脑中缺氧反应基因基础表达增加的原因。
