Enhancement of hippocampal neurogenesis by lithium

Increasing evidence suggests that mood disorders are associated with a redu ction in regional CNS volume and neuronal and glial cell atrophy or loss. L ithium, a mainstay in the treatment of mood disorders, has recently been de monstrated to robustly increase the revels of the cytoprotective B-cell lym phoma protein-2 (bcl-2) in areas of rodent brain and in cultured cells. In view of bcl-2's antiapoptotic and neurotrophic effects, the present study w as undertaken to determine if lithium affects neurogenesis in the adult rod ent hippocampus. Mice were chronically treated with lithium, and 5-bromo-2- deoxyuridine (BrdU) labeling of dividing cells was conducted over 12 days. Immunohistochemical analysis was undertaken 1 day after the last injection, and three-dimensional stereological cell counting revealed that lithium pr oduced a significant 25% increase in the BrdU-labeled cells in the dentate gyrus. Double-labeling immunofluorescence studies were undertaken to co-loc alize BrdU-positive cells with neuron-specific nuclear protein and showed t hat similar to 65% of the cells were double-labeled. These results add to t he growing body of evidence suggesting that mood stabilizers and antidepres sants exert neurotrophic effects and may therefore be of use in the long-te rm treatment of other neuropsychiatric disorders.