Abnormalities of the serotonergic system in diacylglycerol kinase δ-deficient mouse brain.
Abnormalities of the serotonergic system in diacylglycerol kinase δ-deficient mouse brain.
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二酰基甘油激酶 δ 缺陷小鼠大脑中血清素能系统的异常。
DOI：
10.1016/j.bbrc.2018.02.165
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发表时间：
2018
影响因子：
3.1
通讯作者：
F.
中科院分区：
文献类型：
--
作者：
Lu;Q.;Komenoi;S.;Usuki;T.;Takahashi;D.;and Sakane;F.
我们先前报道了脑特异性二酰基甘油激酶（DGK）δ基因敲除（KO）小鼠表现出强迫症（OCD）样行为，这些行为可被5-羟色胺（5-HT）转运体（SERT）抑制剂缓解。然而，导致强迫症样异常行为的分子机制仍不清楚。在本研究中，我们发现DGKδ缺乏增加小鼠大脑皮层中SERT蛋白水平。此外，DGKδ与SERT相互作用并共定位。此外，DGKδ-KO降低色氨酸羟化酶-2的表达，并增加单胺氧化酶-A的表达。事实上，在DGKδ-KO小鼠中大脑皮层中5-HT的量显著降低。这些数据有力地表明，在DGKδ-KO小鼠中的OCD样行为是由全面的和复合的多巴胺能功能低下引起的。
We previously reported that brain-specific diacylglycerol kinase (DGK) δ-knockout (KO) mice showed obsessive-compulsive disorder (OCD)-like behaviors, which were alleviated by a serotonin (5-HT) transporter (SERT) inhibitor. However, the molecular mechanisms causing the OCD-like abnormal behaviors remain unclear. In the present study, we found that DGKδ deficiency increased SERT protein levels in the mouse cerebral cortex. Moreover, DGKδ interacted and co-localized with SERT. Furthermore, DGKδ-KO decreased tryptophan hydroxylase-2 expression and increased monoamine oxidase-A expression. Indeed, the amount of 5-HT in the cerebral cortex was significantly decreased in DGKδ-KO mice. These data strongly suggest that OCD-like behaviors in the DGKδ-KO mice are caused by comprehensive and composite serotonergic hypofunction.