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.
Conclusion:
These findings are partially compatible with reported observations in humans, indicating that PDLIM5 is involved in psychiatric disorders, including mood disorders.
Publication types
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Research Support, Non-U.S. Gov't
MeSH terms
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Adaptor Proteins, Signal Transducing / deficiency*
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Adaptor Proteins, Signal Transducing / genetics*
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Adaptor Proteins, Signal Transducing / metabolism
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Animals
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Behavior, Animal / drug effects
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Bipolar Disorder / genetics
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Bipolar Disorder / metabolism*
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Bipolar Disorder / physiopathology
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Bipolar Disorder / psychology
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Brain / drug effects
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Brain / metabolism
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Brain / physiopathology
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Cell Line
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Depressive Disorder / genetics
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Depressive Disorder / metabolism*
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Depressive Disorder / physiopathology
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Depressive Disorder / psychology
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Gene Expression Regulation / drug effects
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Gene Expression Regulation / genetics
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Gene Knockout Techniques*
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Haloperidol / pharmacology
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Imipramine / pharmacology
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Inhibition, Psychological
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LIM Domain Proteins / deficiency*
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LIM Domain Proteins / genetics*
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LIM Domain Proteins / metabolism
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Male
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Methamphetamine / pharmacology
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Mice
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Microfilament Proteins / deficiency*
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Microfilament Proteins / genetics*
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Microfilament Proteins / metabolism
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Motor Activity / drug effects
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Motor Activity / genetics
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Peptides / pharmacology
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Protein Kinase C-epsilon / antagonists & inhibitors
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Protein Kinase C-epsilon / metabolism
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Protein Transport / drug effects
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Reflex, Startle / drug effects
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Reflex, Startle / genetics
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Swimming
Substances
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Adaptor Proteins, Signal Transducing
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ENH protein, mouse
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LIM Domain Proteins
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Microfilament Proteins
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Peptides
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Methamphetamine
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Protein Kinase C-epsilon
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Haloperidol
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Imipramine
Grants and funding
This work was supported by JSPS KAKENHI (Grant Nos. 23390285 and 10212648) and Grant-in-Aid for Scientific Research on Innovative Areas (23129501) from the Ministry of Education, Culture, Sports, Science and Technology of Japan. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.