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Deficiency of diacylglycerol kinase η induces lithium‐sensitive mania‐like behavior
Author(s) -
Isozaki Takeshi,
Komenoi Suguru,
Lu Qiang,
Usuki Takako,
Tomokata Shuntaro,
Matsutomo Daisuke,
Sakai Hiromichi,
Bando Kana,
Kiyonari Hiroshi,
Sakane Fumio
Publication year - 2016
Publication title -
journal of neurochemistry
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.75
H-Index - 229
eISSN - 1471-4159
pISSN - 0022-3042
DOI - 10.1111/jnc.13661
Subject(s) - diacylglycerol kinase , mania , bipolar disorder , elevated plus maze , lithium (medication) , tail suspension test , knockout mouse , neuroscience , endocrinology , open field , medicine , biology , psychology , behavioural despair test , hippocampus , anxiety , protein kinase c , kinase , psychiatry , microbiology and biotechnology , receptor , antidepressant
The η 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 DGK η in the etiology of bipolar disorder ( BPD ). However, it is still unknown whether DGK η is indeed related to BPD . In this study, we generated DGK η‐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 DGK η deficits on psychomotor behavior. Intriguingly, DGK η‐ 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, DGK η‐ KO mice showed impairment in glycogen synthase kinase ( GSK ) 3β signaling, which is closely related to BPD . These findings clearly support the linkage between BPD and DGK η that is implicated by genome‐wide association studies. Moreover, this study provides DGK η‐ KO mice as a previously unrecognized model that reflects several features of human BPD with manic episodes and revealed an important role for DGK η in regulating behavior and mood through, at least in part, GSK 3β signaling.Several genome‐wide association studies have implicated diacylglycerol kinase (DGK) η gene in the etiology of bipolar disorder (BPD). In this study, we revealed that DGKη‐knockout (KO) mice displayed an overall behavioral profile that is similar to mania of BPD and is lithium (BPD (mania) remedy)‐sensitive. DGKη may regulate behavior and mood through, at least in part, glycogen synthase kinase (GSK) 3β signaling.