Abstract
Abstract Sex hormones are known to play an important role in promoting neuroprotective activity and neurogenesis, but their roles and effects are not yet fully understood. Using zebrafish as a neurogenesis model organism, its brain serves as an excellent research system to study brain repair and the complex neurogenic process. In this study, we aimed to analyze how sex hormones regulate neurogenesis and brain regeneration after traumatic brain injury in adult zebrafish. After generating an injury by needle punch into the adult zebrafish cerebellum, we modified the sex hormonal level through estrogenic treatment or inhibition of 5α-reductase by finasteride treatment. At 3, 6 and 10 days post-injury, we harvested the fish brains for cell proliferation assay by histological analysis, and target gene expression profiling by qPCR assay. We found the mRNA expression level of neurogenesis biomarker gfap, and the key enzyme of estradiol synthesis cyp19a1b, were both down-regulated by finasteride. On the other hand, estradiol treatment increased mRNA expression of gfap and cyp19a1b. Next, we analyzed the expression of other upstream enzymes in the steroid hormone biosynthesis pathway, including cyp17 and 3β-hsd . Surprisingly, finasteride increased cyp17 and 3β-hsd mRNA expression, while estradiol treatment reduced 3β-hsd mRNA expression. The data suggests a feedback regulatory mechanism of estrogen during neurogenesis and brain regeneration. This study confirmed that estrogenic treatment can promote neurogenesis after traumatic brain injury in adult zebrafish. However, inhibition of 5α-reductase activity by finasteride may pose detrimental effect on brain regeneration. Altogether, we concluded that the regulation of steroidogenic enzymes may have a neurogenic switch mechanism on neurogenesis and after traumatic brain injury in zebrafish.