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- Title
Diacylglycerol Kinase β Knockout Mice Exhibit Lithium-Sensitive Behavioral Abnormalities.
- Authors
Kakefuda, Kenichi; Oyagi, Atsushi; Ishisaka, Mitsue; Tsuruma, Kazuhiro; Shimazawa, Masamitsu; Yokota, Koichi; Shirai, Yasuhito; Horie, Kyoji; Saito, Naoaki; Takeda, Junji; Hara, Hideaki
- Abstract
Background: Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). DGKβ is widely distributed in the central nervous system, such as the olfactory bulb, cerebral cortex, striatum, and hippocampus. Recent studies reported that the splice variant at the COOH-terminal of DGKβ was related to bipolar disorder, but its detailed mechanism is still unknown. Methodology/Principal Findings: In the present study, we performed behavioral tests using DGKβ knockout (KO) mice to investigate the effects of DGKβ deficits on psychomotor behavior. DGKβ KO mice exhibited some behavioral abnormalities, such as hyperactivity, reduced anxiety, and reduced depression. Additionally, hyperactivity and reduced anxiety were attenuated by the administration of the mood stabilizer, lithium, but not haloperidol, diazepam, or imipramine. Moreover, DGKβ KO mice showed impairment in Akt-glycogen synthesis kinase (GSK) 3β signaling and cortical spine formation. Conclusions/Significance: These findings suggest that DGKβ KO mice exhibit lithium-sensitive behavioral abnormalities that are, at least in part, due to the impairment of Akt-GSK3β signaling and cortical spine formation.
- Subjects
DIGLYCERIDES; MICE; LITHIUM; ENZYMES; PHOSPHATIDIC acids; CENTRAL nervous system; CEREBRAL cortex
- Publication
PLoS ONE, 2010, Vol 5, Issue 10, p1
- ISSN
1932-6203
- Publication type
Article
- DOI
10.1371/journal.pone.0013447