| First Author | Ishisaka M | Year | 2012 |
| Journal | PLoS One | Volume | 7 |
| Issue | 5 | Pages | e37058 |
| PubMed ID | 22590645 | Mgi Jnum | J:204267 |
| Mgi Id | MGI:5529904 | Doi | 10.1371/journal.pone.0037058 |
| Citation | Ishisaka M, et al. (2012) Diacylglycerol kinase beta knockout mice exhibit attention-deficit behavior and an abnormal response on methylphenidate-induced hyperactivity. PLoS One 7(5):e37058 |
| abstractText | BACKGROUND: Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol to produce phosphatidic acid. DGKbeta is one of the subtypes of the DGK family and regulates many intracellular signaling pathways in the central nervous system. Previously, we demonstrated that DGKbeta knockout (KO) mice showed various dysfunctions of higher brain function, such as cognitive impairment (with lower spine density), hyperactivity, reduced anxiety, and careless behavior. In the present study, we conducted further tests on DGKbeta KO mice in order to investigate the function of DGKbeta in the central nervous system, especially in the pathophysiology of attention deficit hyperactivity disorder (ADHD). METHODOLOGY/PRINCIPAL FINDINGS: DGKbeta KO mice showed attention-deficit behavior in the object-based attention test and it was ameliorated by methylphenidate (MPH, 30 mg/kg, i.p.). In the open field test, DGKbeta KO mice displayed a decreased response to the locomotor stimulating effects of MPH (30 mg/kg, i.p.), but showed a similar response to an N-methyl-d-aspartate (NMDA) receptor antagonist, MK-801 (0.3 mg/kg, i.p.), when compared to WT mice. Examination of the phosphorylation of extracellular signal-regulated kinase (ERK), which is involved in regulation of locomotor activity, indicated that ERK1/2 activation induced by MPH treatment was defective in the striatum of DGKbeta KO mice. CONCLUSIONS/SIGNIFICANCE: These findings suggest that DGKbeta KO mice showed attention-deficit and hyperactive phenotype, similar to ADHD. Furthermore, the hyporesponsiveness of DGKbeta KO mice to MPH was due to dysregulation of ERK phosphorylation, and that DGKbeta has a pivotal involvement in ERK regulation in the striatum. |
