Enhancement of hippocampal neurogenesis by lithium

J Neurochem. 2000 Oct;75(4):1729-34. doi: 10.1046/j.1471-4159.2000.0751729.x.


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 approximately 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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Animals
  • Antigens, Differentiation / metabolism
  • Bromodeoxyuridine
  • Cell Division / drug effects
  • Hippocampus / cytology
  • Hippocampus / drug effects*
  • Hippocampus / metabolism
  • Immunohistochemistry
  • Lithium / pharmacology*
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Nerve Regeneration / drug effects
  • Neurons / cytology
  • Neurons / drug effects*
  • Neurons / metabolism
  • Phenotype
  • Proto-Oncogene Proteins c-bcl-2 / metabolism


  • Antigens, Differentiation
  • Proto-Oncogene Proteins c-bcl-2
  • Lithium
  • Bromodeoxyuridine