Related Experiment Video
Updated: May 12, 2026
Developing a Rat Model for Bipolar Disorder
Published on: May 2, 2025
Experimental evidence for the involvement of PDLIM5 in mood disorders in hetero knockout mice
Yasue Horiuchi1, Maya Ishikawa, Nobuko Kaito
1Department of Medical Genetics, Majors of Medical Sciences, Graduate School of Comprehensive Human Sciences, University of Tsukuba, Tsukuba, Ibaraki, Japan.
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.
Insights
Reduced PDLIM5 levels in mice offered protection against manic-like symptoms induced by methamphetamine. However, lower PDLIM5 levels increased susceptibility to depressive symptoms, suggesting a complex role in mood disorders.
Area of Science:
- Neuroscience
- Genetics
- Psychiatry
Background:
- PDLIM5 (PDZ and LIM domain 5) gene is implicated in mood disorders.
- PDLIM5 expression is altered in bipolar disorder and major depression.
- Methamphetamine (METH) administration models manic and schizophrenia-like behaviors.
Purpose of the Study:
- To investigate the role of PDLIM5 in manic and depressive symptoms.
- To evaluate the effects of reduced PDLIM5 levels on METH-induced behaviors.
Main Methods:
- Utilized PDLIM5 hetero knockout (KO) mice.
- Assessed METH-induced locomotor hyperactivity, prepulse inhibition, and forced swimming.
- Examined effects of imipramine and haloperidol treatments.
Main Results:
- PDLIM5 hetero KO mice showed reduced METH-induced hyperactivity and prepulse inhibition impairment.
- Increased immobility in the forced swimming test in KO mice, reversed by imipramine.
- METH increased, haloperidol decreased, and imipramine increased PDLIM5 mRNA levels in specific brain regions.
Conclusions:
- PDLIM5 plays a role in psychiatric disorders, including mood disorders.
- Reduced PDLIM5 may protect against manic symptoms but increase susceptibility to depression.
