Gene expression patterns of the LDL receptor and its inhibitor Pcsk9 in the adult zebrafish brain suggest a possible role in neurogenesis.

Abstract

The low-density lipoprotein receptor (LDLr) is the first member of a closely related transmembrane protein family. It is known for its involvement in various physiological processes, mainly in the regulation of lipid metabolism, especially in the brains of mammals and zebrafish. In zebrafish, two ldlr genes (ldlra and b) have been identified and their distribution in the brain is not well documented. Recently, the roles of ldlr and its inhibitor pcsk9 in regenerative process after telencephalic brain injury have been discussed. In this study, we explored the expression patterns of these genes during zebrafish development. We found that ldlra expression was detected at the end of the pharyngula period (48 hpf) and increased during the larval stage. Conversely, ldlrb expression was observed from zygotic to larval stages. Using techniques like in situ hybridization and taking advantage of transgenic fish, we demonstrated the widespread distribution of ldlra, ldlrb and pcsk9 in the brain of adult zebrafish. Specifically, these genes were expressed in neurons and neural stem cells and also at lower levels in endothelial cells. As expected, intraperitoneal injection of fluorescent-labelled LDLs resulted in their uptake by cerebral endothelial cells in a homeostatic context, whereas they diffused within the brain parenchyma after telencephalic injury. However, after intracerebroventricular injections into animals, LDL particles were not taken up by neural stem cells. In conclusion, our results provide additional evidence for LDLr expression in the brain of adult zebrafish. These results raise the question of the role of LDLr in the cholesterol/lipid imbalance in cerebral complications.