Title
Enhancement of hippocampal neurogenesis by
lithium.
Source
Journal of Neurochemistry. 75(4):1729-34, 2000 Oct.
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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