title: Experimental evidence for the involvement of PDLIM5 in mood disorders in hetero knockout mice.
abstract: BACKGROUND
  Reports indicate that PDLIM5 is involved in mood disorders. The PDLIM5 (PDZ and LIM domain 5) gene has been genetically associated with mood disorders; it's expression is upregulated in the postmortem brains of patients with bipolar disorder and downregulated in the peripheral lymphocytes of patients with major depression. Acute and chronic methamphetamine (METH) administration may model mania and the evolution of mania into psychotic mania or schizophrenia-like behavioral changes, respectively.
  
  
  METHODS
  To address whether the downregulation of PDLIM5 protects against manic symptoms and cause susceptibility to depressive symptoms, we evaluated the effects of reduced Pdlim5 levels on acute and chronic METH-induced locomotor hyperactivity, prepulse inhibition, and forced swimming by using Pdlim5 hetero knockout (KO) mice.
  
  
  RESULTS
  The homozygous KO of Pdlim5 is embryonic lethal. The effects of METH administration on locomotor hyperactivity and the impairment of prepulse inhibition were lower in Pdlim5 hetero KO mice than in wild-type mice. The transient inhibition of PDLIM5 (achieved by blocking the translocation of protein kinase C epsilon before the METH challenge) had a similar effect on behavior. Pdlim5 hetero KO mice showed increased immobility time in the forced swimming test, which was diminished after the chronic administration of imipramine. Chronic METH treatment increased, whereas chronic haloperidol treatment decreased, Pdlim5 mRNA levels in the prefrontal cortex. Imipramine increased Pdlim5 mRNA levels in the hippocampus.
  
  
  CONCLUSIONS
  These findings are partially compatible with reported observations in humans, indicating that PDLIM5 is involved in psychiatric disorders, including mood disorders.
authors.affiliation: Department of Medical Genetics, Majors of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
authors.forename: Yasue
authors.initials: Y
authors.lastname: Horiuchi
authors.forename: Maya
authors.initials: M
authors.lastname: Ishikawa
authors.forename: Nobuko
authors.initials: N
authors.lastname: Kaito
authors.forename: Yoshimi
authors.initials: Y
authors.lastname: Iijima
authors.forename: Yoshiko
authors.initials: Y
authors.lastname: Tanabe
authors.forename: Hiroki
authors.initials: H
authors.lastname: Ishiguro
authors.forename: Tadao
authors.initials: T
authors.lastname: Arinami
mesh_terms: D048868:Adaptor Proteins, Signal Transducing / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D001714:Bipolar Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D001921:Brain / Q000187:drug effects / Q000378:metabolism / Q000503:physiopathology; D002460:Cell Line; D003866:Depressive Disorder / Q000235:genetics / Q000378:metabolism* / Q000503:physiopathology / Q000523:psychology; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D055786:Gene Knockout Techniques; D006220:Haloperidol / Q000494:pharmacology; D007099:Imipramine / Q000494:pharmacology; D007266:Inhibition, Psychological; D060588:LIM Domain Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D008297:Male; D008694:Methamphetamine / Q000494:pharmacology; D051379:Mice; D008840:Microfilament Proteins / Q000172:deficiency* / Q000235:genetics* / Q000378:metabolism; D009043:Motor Activity / Q000187:drug effects / Q000235:genetics; D010455:Peptides / Q000494:pharmacology; D051744:Protein Kinase C-epsilon / Q000037:antagonists & inhibitors / Q000378:metabolism; D021381:Protein Transport / Q000187:drug effects; D013216:Reflex, Startle / Q000187:drug effects / Q000235:genetics; D013550:Swimming
chemical_list: D048868:Adaptor Proteins, Signal Transducing; C510085:ENH protein, mouse; D060588:LIM Domain Proteins; D008840:Microfilament Proteins; D010455:Peptides; D008694:Methamphetamine; D051744:Protein Kinase C-epsilon; D006220:Haloperidol; D007099:Imipramine