Cell proliferation pattern in adult zebrafish forebrain is sexually dimorphic

Cell proliferation, differentiation and cell death are considered key players for brain plasticity mechanisms that underlie sex specific phenotypes in brain and behavior. Well-documented examples of sex-specific neurogenesis are the avian song system telencephalic areas and the mammalian hippocampus. The present study questioned whether sex difference in cell proliferation represents a conserved feature of adult brain plasticity, using the neurogenetic model organism zebrafish (Danio rerio). For this, active cycling progenitors were determined by means of 5'-bromo-2'-deoxyuridine (BrdU) immunohistochemistry, in adult male and female zebrafish forebrain proliferation zones. In addition, apoptotic figures were measured using terminal deoxynucleotidyl transferase (TdT)-mediated dUTP nick-end labeling method. Short-term survival experiments showed that the medial zone of dorsal telencephalic area (Dm) the ventral part of periventricular pretectal nucleus (PPv) and the periventricular nucleus of posterior tuberculum, exhibited higher levels of cycling cells in females, while the dorsal zone of periventricular hypothalamus displayed higher density of mitotically active cells in males. Apoptotic figures were present in all major proliferation zones, but did not differ between sexes. However, apoptotic figures paralleled the density of dividing cells, suggesting a close relationship of cell birth and cell death. Interestingly, in long-term survival experiments, sex differences were preserved in the long-lasting BrdU cells within the telencephalic Dm (homologous to mammalian amygdala), and the diencephalic PPv, areas that have a role in emotional behavior and endocrine regulation. The present data suggest that sex-specific patterns of proliferating progenitors may represent an important mechanism for the development of sex differences of adult brain.