Abstract
Background: Substantial evidence indicates that lithium may exert its therapeutic
effects through progressive adaptive changes at the level of gene expression; however,
the study of lithium-regulated genes has been primarily undertaken with the “candidate
gene” approach based on a specific testable hypothesis. The aim of our study was to
identify lithium-regulated genes that would not be predicted a priori by the candidate
gene approach.
Methods: Differential display polymerase chain reaction was used to isolate and identify
messenger RNAs (mRNAs) that are differentially expressed in the frontal cortex of
rats given lithium for 5 weeks to achieve plasma lithium concentrations of 0.6 to
0.9 mmol/L.
Results: A putative lithium-regulated complementary DNA fragment (LRG1) was identified.
Northern blot analysis revealed that 5 weeks of lithium treatment, but not 1 week,
significantly reduced LRG1 mRNA levels. LRG1 mRNA levels were similarly reduced by
5 weeks of carbamazepine, but not valproate administration. Sequence analysis and
search of the GenBank database revealed that LRG1 is analogous to the sequence of
the gene for rat aldolase A.
Conclusions: These results demonstrate that chronic administration of lithium, but
not short-term administration, downregulates the levels of aldolase A mRNA, suggesting
this effect may play a role in mediating the therapeutic action of this agent.
Keywords
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Article info
Publication history
Accepted:
February 7,
2000
Received in revised form:
February 2,
2000
Received:
October 12,
1999
Identification
Copyright
© 2000 Society of Biological Psychiatry. Published by Elsevier Inc. All rights reserved.
