Sex-dependent regulation of hippocampal neurogenesis under basal and chronic stress conditions in rats.

Sex differences in basal as well as in stress-induced hippocampal neurogenesis processes have been reported in the literature. However, studies directly comparing sex differences on multiple neurogenesis processes under such conditions are lacking to date. Therefore, the aim of the present study was to directly compare cell proliferation and survival, neuronal and astroglial differentiation as well as stem cells quiescence in male and female Wistar rats under both basal and chronic stress conditions (12 days of 2 h restraint stress (RS)). In addition, corticosterone (CORT) levels and spatial working memory were assessed. Under baseline conditions, only the number of immature neurons within the hippocampal dentate gyrus was higher in males compared with females. In contrast, chronic stress resulted in a number of sex-specific alterations. Thus, stress exposure reduced cell proliferation in males with a concurrent increase in stem cell quiescence, while it did not alter either parameter in females but decreased cell survival. Analysis of astroglial and neuronal differentiation patterns revealed that chronic stress specifically diminished the number of mature neurons in females, with no effect in males. Despite the observed sex differences in adult hippocampal neurogenesis, spatial working memory was not altered by stress exposure in either sex. While basal CORT levels were higher, chronic stress exposure did not affect this parameter in either sex across the initial stress period. This study presents the first direct and detailed evaluation of sex-dependent and chronic stress-induced changes in adult hippocampal neurogenesis not only showing changes in cell proliferation and survival, but moreover immature neuron production, differentiation patterns, stem cell quiescence and therefore contributes to a better understanding of sex differences in neurogenesis processes.