title: Memantine, an NMDA receptor antagonist, improves working memory deficits in DGKβ knockout mice.
abstract: Diacylglycerol kinase (DGK) β is a type 1 isozyme of the DGK family. We previously reported that DGKβ was deeply involved in neurite spine formation, and DGKβ 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 DGKβ KO mice. In the present study, we evaluated the effect of an anti-Alzheimer's drug, memantine on the working memory deficit observed in DGKβ KO mice. In the Y-maze test, the administration of memantine significantly improved working memory of DGKβ 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 DGKβ 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 DGKβ has a pivotal role in cognitive function.
authors: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
authors: Kenichi
authors: K
authors: Kakefuda
authors: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
authors: Mitsue
authors: M
authors: Ishisaka
authors: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
authors: Kazuhiro
authors: K
authors: Tsuruma
authors: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan.
authors: Masamitsu
authors: M
authors: Shimazawa
authors: Department of Biofunctional Evaluation, Molecular Pharmacology, Gifu Pharmaceutical University, Gifu, Japan. Electronic address: hidehara@gifu-pu.ac.jp.
authors: Hideaki
authors: H
authors: Hara
mesh_terms: D000818:Animals; D019852:Diacylglycerol Kinase / Q000235:genetics / Q000502:physiology*; D018691:Excitatory Amino Acid Antagonists / Q000008:administration & dosage*; D006624:Hippocampus / Q000378:metabolism; D008297:Male; D018782:Maze Learning / Q000187:drug effects / Q000502:physiology; D008559:Memantine / Q000008:administration & dosage*; D008570:Memory, Short-Term / Q000187:drug effects* / Q000502:physiology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D017397:Prefrontal Cortex / Q000378:metabolism; D016194:Receptors, N-Methyl-D-Aspartate / Q000819:agonists* / Q000378:metabolism
chemical_list: D018691:Excitatory Amino Acid Antagonists; C120997:NR2A NMDA receptor; C121001:NR2B NMDA receptor; D016194:Receptors, N-Methyl-D-Aspartate; D019852:Diacylglycerol Kinase; D008559:Memantine
keywords: DGKβ; Memantine; NMDA; Working memory