Jia Yun-Fang, Wininger Katheryn, Ho Ada Man-Choi, Peyton Lee, Baker Matthew, Choi Doo-Sup
Department of Molecular Pharmacology and Experimental Therapeutic, Mayo Clinic, Rochester, MN, United States.
Neuroscience Program, Mayo Clinic, Rochester, MN, United States.
Front Behav Neurosci. 2020 Apr 22;14:57. doi: 10.3389/fnbeh.2020.00057. eCollection 2020.
Glutamatergic dysregulation is known to contribute to altered emotional regulation. Astrocytic glutamate transporter 1 (GLT1) is responsible for the majority of glutamate clearance from synapse. However, the role of astrocytic GLT1 in affective processes such as anxiety- and depression-like behavior is not fully understood. Here, we found that astrocytic GLT1 deficient mice entered more frequently, and spent more time in the open arms of elevated plus maze without difference in overall distance traveled in the open field, nor were there any metabolic changes observed in the metabolic chamber compared to wildtype mice. Moreover, mice lacking astrocytic GLT1 exhibited less immobile time and moved greater area in the tail suspension test. Similarly, in the forced swim test, they showed less immobile time and moved greater area. In addition, we found that astrocytic GLT1 deficiency reduced freezing responses in the fear contextual and cued tests. Taken together, our findings suggest that astrocytic GLT1 deficiency decreases anxiety and depression-like behaviors.
已知谷氨酸能调节异常会导致情绪调节改变。星形胶质细胞谷氨酸转运体1(GLT1)负责从突触清除大部分谷氨酸。然而,星形胶质细胞GLT1在诸如焦虑样和抑郁样行为等情感过程中的作用尚未完全明确。在此,我们发现星形胶质细胞GLT1缺陷小鼠更频繁地进入高架十字迷宫的开放臂,并且在开放臂中停留的时间更长,在旷场试验中总的行进距离没有差异,与野生型小鼠相比,在代谢室中也未观察到任何代谢变化。此外,缺乏星形胶质细胞GLT1的小鼠在悬尾试验中表现出更少的不动时间,移动面积更大。同样,在强迫游泳试验中,它们也表现出更少的不动时间,移动面积更大。此外,我们发现星形胶质细胞GLT1缺陷会降低恐惧情境和线索试验中的僵住反应。综上所述,我们的研究结果表明,星形胶质细胞GLT1缺陷会减少焦虑样和抑郁样行为。