Lu Qiang, Komenoi Suguru, Usuki Takako, Takahashi Daisuke, Sakane Fumio
Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Department of Chemistry, Graduate School of Science, Chiba University, 1-33 Yayoi-cho, Inage-ku, Chiba 263-8522, Japan.
Biochem Biophys Res Commun. 2018 Mar 18;497(4):1031-1037. doi: 10.1016/j.bbrc.2018.02.165. Epub 2018 Feb 24.
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.
我们之前报道过，脑特异性二酰甘油激酶（DGK）δ基因敲除（KO）小鼠表现出类似强迫症（OCD）的行为，而血清素（5-HT）转运体（SERT）抑制剂可缓解这些行为。然而，导致类似OCD异常行为的分子机制仍不清楚。在本研究中，我们发现DGKδ缺乏会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基因敲除会降低色氨酸羟化酶-2的表达并增加单胺氧化酶-A的表达。实际上，DGKδ基因敲除小鼠大脑皮层中的5-HT含量显著降低。这些数据有力地表明，DGKδ基因敲除小鼠中类似OCD的行为是由全面和复合的血清素能功能减退引起的。
