Mapping cellular gains and losses in the postnatal dentate gyrus: implications for psychiatric disorders

Neurogenesis and apoptosis occur contemporaneously in the postnatal hippocampal dentate gyrus and have been implicated in mood and cognitive disorders. Particularly, neurogenesis correlates with the manifestation of antidepressant effects, but its quantitative and topographical relationship with concomitant cell death has not been investigated. Accordingly, we applied stereological measurements to obtain synchronized topographical maps of these two events in rats aged 1 and 3 months under basal conditions; the two ages were chosen to represent neuro-developmental windows during which cell proliferation and death are occurring at peak and relatively steady levels, respectively. Our analysis shows that apoptotic cells are evenly distributed throughout the dentate gyrus, although the incidence of apoptosis decreased gradient-wise from the tip of the suprapyramidal layer and was highest in the external third of the granule cell layer. Interestingly, apoptosis was higher in the left hippocampus. In addition, we confirm previous less stringent studies demonstrating that neurogenesis occurs differentially in the dorsal-ventral axis of the hippocampus and in suprapyramidal-infrapyramidal blades of the dentate gyrus. These results raise intriguing new questions regarding the coordinated regulation of hippocampal neurogenesis and apoptosis since the two processes apparently share common regulatory factors. In addition, these findings open questions with respect to the functional significance of topographical gradients in neurogenesis and apoptosis in the context of the etiopathogenesis of neuropsychiatric diseases and the reported dependence on the efficacy of therapeutic agents on the generation of new hippocampal neurons.This work was partly supported by an exchange grant from GRICES/DAAD (423/DAAD). Rui Silva is a pre-doctoral fellow of the Portuguese Foundation for Science and Technology (SFRH/BD/9756/2003). Jie Lu and Yan Wu were supported by fellowships from the Max Planck Society