title: Microarray gene expression profiling of mouse brain mRNA in a model of lithium treatment.
abstract: OBJECTIVE
  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).
  
  
  CONCLUSIONS
  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 cellular pathways in the brain. Understanding the molecular and cellular mechanisms by which lithium achieves its therapeutic action represents a valuable step in clarifying the pathophysiology of bipolar disorder.
authors: Schizophrenia Research Institute, Sydney, New South Wales, Australia.
authors: Albert
authors: A
authors: Chetcuti
authors: Linda J
authors: LJ
authors: Adams
authors: Philip B
authors: PB
authors: Mitchell
authors: Peter R
authors: PR
authors: Schofield
mesh_terms: D000818:Animals; D001923:Brain Chemistry / Q000187:drug effects*; D000075065:Elongin; D044387:GTP-Binding Protein beta Subunits; D020869:Gene Expression Profiling; D005786:Gene Expression Regulation / Q000187:drug effects*; D020962:Heterotrimeric GTP-Binding Proteins / Q000096:biosynthesis / Q000235:genetics; D018021:Lithium Chloride / Q000494:pharmacology*; D008297:Male; D000090023:Metallothionein 3; D051379:Mice; D008810:Mice, Inbred C57BL; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics*; D020411:Oligonucleotide Array Sequence Analysis; D046988:Proteasome Endopeptidase Complex / Q000096:biosynthesis / Q000235:genetics; D012333:RNA, Messenger / Q000096:biosynthesis*; D000254:Sodium-Potassium-Exchanging ATPase / Q000096:biosynthesis / Q000235:genetics; D014157:Transcription Factors / Q000096:biosynthesis / Q000235:genetics
chemical_list: C000616396:ELOB protein, human; C000616401:Elob protein, mouse; D000075065:Elongin; D044387:GTP-Binding Protein beta Subunits; C491082:Gnb1 protein, mouse; D000090023:Metallothionein 3; C000715430:Mt3 protein, mouse; D009419:Nerve Tissue Proteins; D012333:RNA, Messenger; D014157:Transcription Factors; D046988:Proteasome Endopeptidase Complex; C478802:Psmb5 protein, mouse; C499076:ATP1A1 protein, human; D020962:Heterotrimeric GTP-Binding Proteins; D000254:Sodium-Potassium-Exchanging ATPase; D018021:Lithium Chloride