Age-Dependent Regulation of Neurogenesis and Memory by Dbc1

The protein Dbc1 participates in multiple cellular processes, including transcriptional regulation, DNA damage repair, metabolic modulation, and cell cycle regulation. These functions are mediated through its physical interaction with target proteins, thereby regulating their biological activity. Using constitutive whole body Dbc1 knockout adult mice, we observed impaired neurogenesis in the dentate gyrus (DG), accompanied by specific behavioral alterations. However, it remains unclear whether these effects are due to a direct role of Dbc1 in regulating DG neurogenesis or to indirect consequences of its absence in other regions of the nervous system. In this study, we investigated the specific role of Dbc1 in regulating the cell cycle of neuronal precursors in the DG and its potential impact on cognitive functions. We employed a conditional Dbc1fl/fl mouse model under the control of a nestin promoter and inducible by tamoxifen, allowing the selective deletion of Dbc1 in DG neuronal precursors. DG neuroblasts were quantified using a marker of immature neurons, while neural progenitor status and the degree of neuronal differentiation were assessed based on relative mRNA expression. Cognitive performance was additionally evaluated using different behavioral tests. Our results demonstrate that the effects of Dbc1 deletion are age dependent. As expected, Dbc1 deletion was associated with reduced neurogenesis in 6–8-week-old animals, an effect that was lost in 10–12-week-old mice.