http://www.ncbi.nlm.nih.gov/pubmed/10987856
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 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.
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