Memantine, an NMDA receptor antagonist, improves working memory deficits in DGKß knockout mice.

Diacylglycerol kinase (DGK) ß is a type 1 isozyme of the DGK family. We previously reported that DGKß was deeply involved in neurite spine formation, and DGKß knockout (KO) mice exhibited behavioral abnormalities concerning spine formation, such as cognitive, emotional, and attentional impairment. Moreover, some of these abnormalities were ameliorated by the administration of a mood stabilizer. However, there is no data about how memory-improving drugs used in the treatment of Alzheimer's disease affect DGKß KO mice. In the present study, we evaluated the effect of an anti-Alzheimer's drug, memantine on the working memory deficit observed in DGKß KO mice. In the Y-maze test, the administration of memantine significantly improved working memory of DGKß KO mice. We also found that the expression levels of the NR2A and NR2B N-methyl-d-aspartate (NMDA) receptor subunits were increased in the prefrontal cortex, but decreased in the hippocampus of DGKß KO mice. These altered expression levels of NR2 subunits might be related to the effect of an NMDA receptor antagonist, memantine. Taken together, these findings may support the hypothesis that DGKß has a pivotal role in cognitive function.