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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.    Conclusion  These findings are partially compatible with reported observations in humans, indicating that PDLIM5 is involved in psychiatric disorders, including mood disorders.

Experimental Evidence for the Involvement of PDLIM5 in Mood Disorders in Hetero Knockout Mice