Diacylglycerol Kinase β Knockout Mice Exhibit Lithium-Sensitive Behavioral Abnormalities
Diacylglycerol Kinase β Knockout Mice Exhibit Lithium-Sensitive Behavioral Abnormalities
复制标题
DOI：
10.1371/journal.pone.0013447
复制
发表时间：
2010-10-18
期刊：
影响因子：
3.7
通讯作者：
Hara, Hideaki
中科院分区：
文献类型：
--
作者：
Kakefuda, Kenichi;Oyagi, Atsushi;Hara, Hideaki
背景：甘油二酯激酶（DGK）是一种磷酸化甘油二酯（DG）生成磷脂酸（PA）的酶。DGK β广泛分布于中枢神经系统，如嗅球、大脑皮层、纹状体和海马。最近的研究报道，剪接变异体在COOH-末端的DGK β相关的双相情感障碍，但其详细的机制仍然是unknowed.Methodology/主要调查结果：在本研究中，我们进行了行为测试，使用DGK β基因敲除（KO）小鼠调查的影响DGK β赤字对精神行为。DGK β KO小鼠表现出一些行为异常，如多动、焦虑减轻和抑郁减轻。此外，多动和焦虑减少减弱的情绪稳定剂，锂，但不是氟哌啶醇，地西泮，或丙咪嗪的管理。此外，DGK β KO小鼠表现出Akt-糖原合成激酶（GSK）3 β信号传导和皮质棘formation.Conclusions/Significance损伤：这些发现表明，DGK β KO小鼠表现出锂敏感性行为异常，至少部分是由于Akt-GSK 3 β信号传导和皮质棘形成的损伤。
Background: Diacylglycerol kinase (DGK) is an enzyme that phosphorylates diacylglycerol (DG) to produce phosphatidic acid (PA). DGK beta 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 beta 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 beta knockout (KO) mice to investigate the effects of DGK beta deficits on psychomotor behavior. DGK beta 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 beta KO mice showed impairment in Akt-glycogen synthesis kinase (GSK) 3 beta signaling and cortical spine formation.Conclusions/Significance: These findings suggest that DGK beta KO mice exhibit lithium-sensitive behavioral abnormalities that are, at least in part, due to the impairment of Akt- GSK3 beta signaling and cortical spine formation.