Cyclosporin A enhances neurogenesis in the dentate gyrus of the hippocampus

• Cyclosporin A increases the numbers but not the size of clonally derived neurospheres derived from the hippocampus.
• Cyclosporin A enriches for multipotential neurospheres in vitro.
• Infusion of cyclosporin A in vivo promotes neurosphere formation in vitro.
• Cyclosporin A infusion increases proliferation of neural precursor cells and neurogenesis in the dentate gyrus.

Neural precursor cells (NPCs) in the adult mammalian brain demonstrate potential in applications of neural repair in the CNS. Recent work has shown that cyclosporin A (CsA), a commonly used immunosuppressive drug, expands the size of the NPC pool in the subventricular region by promoting cell survival. We asked if CsA had similar effects on NPCs in the dentate gyrus (DG) of the hippocampus, leading to increased neurogenesis. We used the in vitro and in vivo assays to examine CsA's effect on the size of the NPC pool and the proliferation and differentiation profile of cells within the DG. We found that CsA increases the numbers of NPCs and enriches for neurogenic NPCs in vitro. Similarly, in vivo systemic administration of CsA for 7 days increases the size of the NPC pool in the DG observed through increases in numbers of proliferating cells and newborn neurons. Consistent with CsA's pro-survival effects, we have shown that CsA enhances the survival of newborn cells that normally undergo cell death over the time of infusion. Together these findings support the hypothesis that CsA administration promotes neurogenesis and may have implications for neural repair.