Diacylglycerol Kinase β Knockout Mice Exhibit Lithium-Sensitive Behavioral AbnormalitiesReportar como inadecuado




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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.



Autor: Kenichi Kakefuda, Atsushi Oyagi, Mitsue Ishisaka, Kazuhiro Tsuruma, Masamitsu Shimazawa, Koichi Yokota, Yasuhito Shirai, Kyoji Ho

Fuente: http://plos.srce.hr/



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