Deficiency of diacylglycerol kinase η induces lithium-sensitive mania-like behavior.

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 DGKη in the etiology of bipolar disorder (BPD). However, it is still unknown whether DGKη is indeed related to BPD. In this study, we generated DGKη-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 DGKη deficits on psychomotor behavior. Intriguingly, DGKη-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, DGKη-KO mice showed impairment in glycogen synthase kinase (GSK) 3ß signaling, which is closely related to BPD. These findings clearly support the linkage between BPD and DGKη that is implicated by genome-wide association studies. Moreover, this study provides DGKη-KO mice as a previously unrecognized model that reflects several features of human BPD with manic episodes and revealed an important role for DGKη in regulating behavior and mood through, at least in part, GSK3ß 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) 3ß signaling.

Effect of Adding Lecithin and Nonionic Surfactant on α-Gels Based on a Cationic Surfactant-Fatty Alcohol Mixture.

α-Gels are often used as base materials for cosmetics and hair conditioners. α-Gel-based commercial products typically contain many types of additives, such as polymers, electrolytes, oily components, and other surfactants, in addition to the three basic components. However, few systematic studies have been conducted on the effect of such additives on α-gels. In this study, we chose surfactant as an example to initiate the effect of such additives on the structure and rheological properties of α-gel samples formulated using cetyl alcohol (C16OH) and cetyltrimethylammonium chloride (CTAC). Optical microscopy analysis demonstrated that the size of the vesicles in the α-gel samples in this study was decreased via the addition of hydrogenated soybean lecithin (HSL) and penta(oxyethylene) cetyl ether (C16EO5), a nonionic surfactant, to them. Rheological measurements revealed that at high C16OH/CTAC ratios, the viscosity and yield stress of the α-gel samples decreased owing to the addition of surfactants to them. Conversely, at low C16OH/CTAC ratios, the opposite tendency was observed. Small-angle X-ray scattering analysis indicated that for the α-gel samples with high C16OH/CTAC ratios, the addition of HSL or C16EO5 to them decreased the interlayer spacing of their lamellar bilayer stack, which led to the changes in the rheological properties of the α-gel samples.

Osmotic shock-dependent redistribution of diacylglycerol kinase η1 to non-ionic detergent-resistant membrane via pleckstrin homology and C1 domains.

Diacylglycerol kinase (DGK) participates in regulating the intracellular concentrations of two bioactive lipids, diacylglycerol and phosphatidic acid. DGKη1 is a type II isozyme that contains a pleckstrin homology (PH) domain and a pair of C1 domains at the N-terminus and separated catalytic domains (catalytic subdomain-a and b). We previously reported that DGKη1 expressed in COS-7 cells is translocated from the cytoplasm to punctate granules that partially include endosomes in response to stress stimuli such as osmotic shock. However, the biochemical properties of the stress-dependent behaviour of DGKη1 remain unknown. Here, we have found that DGKη1 is redistributed from the cytosol to the non-ionic detergent (Nonidet P-40)-resistant membrane (DRM) in response to osmotic shock. Our results strongly suggested that the Nonidet P-40 insolubility of DGKη1 is due to neither cytoskeleton localization nor lipid raft association, implying that DGKη1 is distributed to detergent-resistant membrane microdomains that have a low lipid-to-protein ratio. We revealed, using a series of DGKη1 deletion mutants, that the PH and C1 domains play a pivotal role in osmotic shock-dependent DRM redistribution, whereas catalytic subdomain-a negatively regulates the event.