Enhancement of Hippocampal Neurogenesis by Lithium

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Abstract
Increasing evidence suggests that mood disorders are associated with a reduction in regional CNS volume and neuronal and glial cell atrophy or loss. Lithium, a mainstay in the treatment of mood disorders, has recently been demonstrated to robustly increase the levels of the cytoprotective B‐cell lymphoma 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 was undertaken to determine if lithium affects neurogenesis in the adult rodent 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 produced a significant 25% increase in the BrdU‐labeled cells in the dentate gyrus. Double‐labeling immunofluorescence studies were undertaken to co‐localize BrdU‐positive cells with neuron‐specific nuclear protein and showed that ∼65% of the cells were double‐labeled. These results add to the growing body of evidence suggesting that mood stabilizers and antidepressants exert neurotrophic effects and may therefore be of use in the long‐term treatment of other neuropsychiatric disorders.