Diacylglycerol kinase ? knockout mice exhibit lithium-sensitive behavioral abnormalities.

ABSTRACT:

Background

Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). DGK? 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 DGK? was related to bipolar disorder, but its detailed mechanism is still unknown.

Methodology/principal findings

In the present study, we performed behavioral tests using DGK? knockout (KO) mice to investigate the effects of DGK? deficits on psychomotor behavior. DGK? 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, DGK? KO mice showed impairment in Akt-glycogen synthesis kinase (GSK) 3? signaling and cortical spine formation.

Conclusions/significance

These findings suggest that DGK? KO mice exhibit lithium-sensitive behavioral abnormalities that are, at least in part, due to the impairment of Akt-GSK3? signaling and cortical spine formation.

SUBMITTER: Kakefuda K 

PROVIDER: S-EPMC2956634 | biostudies-literature | 2010 Oct

REPOSITORIES: biostudies-literature