| First Author | Isozaki T | Year | 2016 |
| Journal | J Neurochem | Volume | 138 |
| Issue | 3 | Pages | 448-56 |
| PubMed ID | 27167678 | Mgi Jnum | J:234190 |
| Mgi Id | MGI:5789472 | Doi | 10.1111/jnc.13661 |
| Citation | Isozaki T, et al. (2016) Deficiency of diacylglycerol kinase eta induces lithium-sensitive mania-like behavior. J Neurochem 138(3):448-56 |
| abstractText | The eta isozyme of diacylglycerol kinase (DGK) is highly expressed in the hippocampus and Purkinje cells in the central nervous system. Recently, several genome-wide association studies have implicated DGKeta in the etiology of bipolar disorder (BPD). However, it is still unknown whether DGKeta is indeed related to BPD. In this study, we generated DGKeta-knockout (KO) mice and performed behavioral tests such as the open field test, the elevated plus maze test and tail suspension test using the KO mice to investigate the effects of DGKeta deficits on psychomotor behavior. Intriguingly, DGKeta-KO mice displayed an overall behavioral profile that is similar to human mania, including hyperactivity, less anxiety and less depression-like behavior. In addition, these phenotypes were significantly attenuated by the administration of a BPD (mania) remedy, namely, lithium. Moreover, DGKeta-KO mice showed impairment in glycogen synthase kinase (GSK) 3beta signaling, which is closely related to BPD. These findings clearly support the linkage between BPD and DGKeta that is implicated by genome-wide association studies. Moreover, this study provides DGKeta-KO mice as a previously unrecognized model that reflects several features of human BPD with manic episodes and revealed an important role for DGKeta in regulating behavior and mood through, at least in part, GSK3beta signaling. Several genome-wide association studies have implicated diacylglycerol kinase (DGK) eta gene in the etiology of bipolar disorder (BPD). In this study, we revealed that DGKeta-knockout (KO) mice displayed an overall behavioral profile that is similar to mania of BPD and is lithium (BPD (mania) remedy)-sensitive. DGKeta may regulate behavior and mood through, at least in part, glycogen synthase kinase (GSK) 3beta signaling. |
