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Microarray gene expression profiling of mouse brain mRNA in a model of lithium treatment

Chetcuti, Albert, Adams, Linda J., Mitchell, Philip B., Schofield, Peter R.·2008·Psychiatric Genetics
DOI 10.1097/ypg.0b013e3282fb0051
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Abstract

Objectives Even after five decades of use, the mood stabilizer lithium continues to be the mainstay of treatment for bipolar disorder in many countries. The mechanism of action for lithium, however, remains unclear. Methods In this study, microarray analysis was used to identify genes and cellular pathways that are altered in the mouse brain after treatment with lithium at human therapeutic concentrations. Mice received daily injections of lithium chloride for 7 consecutive days. Whole-brain total RNA was used as a template for microarray gene expression profiling. Results This study has identified 19 transcripts that are differentially expressed by four-fold when compared with control untreated mice. The altered expression of these genes was validated by quantitative PCR analysis with five genes showing significant differential expression. Lithium was found to significantly decrease the expression of metallothionein 3 (MT3), ATPase, Na/K transporting, alpha1 polypeptide (ATP1A1), transcription elongation factor B (SIII)-polypeptide 2 (TCEB2), proteasome subunit beta type 5 (PSMB5), and guanine nucleotide binding protein beta1 (GNB1). Conclusion These genes are involved in a diverse range of biological functions, including maintaining metal ion homeostasis and chemical/electrical gradients across membranes, regulating RNA polymerase II, protein degradation, and G-protein-coupled signal transduction. These results indicate that lithium can regulate a large number of different…

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Metadata

Authors
Chetcuti, A., Adams, L. J., Mitchell, P. B., & Schofield, P. R.
Venue
Psychiatric Genetics
Publisher
Ovid Technologies (Wolters Kluwer Health)
Published
2008-04
Volume
18
Issue
2
Pages
64-72
ISSN
0955-8829
DOI
10.1097/ypg.0b013e3282fb0051
Cited by
41
References
1
Language
en

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