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Published on: January 28, 2012
Diacylglycerol kinase β knockout mice exhibit lithium-sensitive behavioral abnormalities
Kenichi Kakefuda1, Atsushi Oyagi, Mitsue Ishisaka
1Molecular Pharmacology, Department of Biofunctional Evaluation, Gifu Pharmaceutical University, Gifu, Japan.
Plos One
|October 27, 2010
Summary
Diacylglycerol kinase beta (DGKβ) deficiency in mice caused hyperactivity, reduced anxiety, and depression. These lithium-sensitive behavioral changes were linked to impaired Akt-GSK3β signaling and cortical spine formation.
Area of Science:
- Neuroscience
- Biochemistry
- Genetics
Background:
- Diacylglycerol kinase (DGK) enzymes produce phosphatidic acid (PA) from diacylglycerol (DG).
- DGKβ is prevalent in brain regions like the hippocampus and cortex.
- DGKβ splice variants are implicated in bipolar disorder, yet mechanisms remain unclear.
Purpose of the Study:
- To investigate the behavioral effects of DGKβ deficiency.
- To explore the underlying molecular mechanisms and potential therapeutic targets.
Main Methods:
- Utilized DGKβ knockout (KO) mouse models for behavioral testing.
- Administered various psychotropic medications including lithium, haloperidol, diazepam, and imipramine.
- Assessed Akt-glycogen synthesis kinase (GSK) 3β signaling pathways and cortical spine formation.
Main Results:
- DGKβ KO mice displayed hyperactivity, reduced anxiety, and decreased depression.
- Lithium administration attenuated hyperactivity and reduced anxiety in KO mice.
- Impaired Akt-GSK3β signaling and reduced cortical spine formation were observed in DGKβ KO mice.
Conclusions:
- DGKβ deficiency leads to specific behavioral abnormalities in mice.
- These abnormalities are sensitive to lithium treatment.
- Impaired Akt-GSK3β signaling and cortical spine deficits contribute to the observed phenotypes.
