Division of Oral Biochemistry, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514, Japan.
Research Center for Advanced Oral Science, Faculty of Dentistry & Graduate School of Medical and Dental Sciences, Niigata University, Niigata, 951-8514, Japan.
Sci Rep. 2024 Feb 24;14(1):4521. doi: 10.1038/s41598-024-55063-z.
Kainate receptors (KARs) are one of the ionotropic glutamate receptors in the central nervous system (CNS) comprised of five subunits, GluK1-GluK5. There is a growing interest in the association between KARs and psychiatric disorders, and there have been several studies investigating the behavioral phenotypes of KAR deficient mice, however, the difference in the genetic background has been found to affect phenotype in multiple mouse models of human diseases. Here, we examined GluK1-5 single KO mice in a pure C57BL/6N background and identified that GluK3 KO mice specifically express anxiolytic-like behavior with an alteration in dopamine D2 receptor (D2R)-induced anxiety, and reduced D2R expression in the striatum. Biochemical studies in the mouse cortex confirmed that GluK3 subunits do not assemble with GluK4 and GluK5 subunits, that can be activated by lower concentration of agonists. Overall, we found that GluK3-containing KARs function to express anxiety, which may represent promising anti-anxiety medication targets.
kainate 受体(KARs)是中枢神经系统(CNS)中的离子型谷氨酸受体之一,由 5 个亚基组成,GluK1-GluK5。越来越多的人关注 KARs 与精神疾病之间的关联,已经有几项研究调查了 KAR 缺失小鼠的行为表型,然而,在多种人类疾病的小鼠模型中,遗传背景的差异已被发现会影响表型。在这里,我们在纯 C57BL/6N 背景下检查了 GluK1-5 单 KO 小鼠,并发现 GluK3 KO 小鼠特异性表现出焦虑样行为,多巴胺 D2 受体(D2R)诱导的焦虑发生改变,纹状体中 D2R 表达减少。在小鼠皮层中的生化研究证实,GluK3 亚基不能与 GluK4 和 GluK5 亚基组装,而这些亚基可以被较低浓度的激动剂激活。总的来说,我们发现含有 GluK3 的 KAR 具有表达焦虑的功能,这可能代表有希望的抗焦虑药物靶点。