Light augments antidepressant response via astroglial modulation of lateral habenula. Light augments antidepressant response via astroglial modulation of lateral habenula

Successful antidepressant treatments are still difficult to achieve. Recently, bright light stimulation (BLS) was shown effective in non-seasonal depression but its mode of action remains elusive. We demonstrate, using a new mouse model of depression resistant to antidepressants including ketamine, that both chemogenetic activation of lateral habenula (LHb) astroglia and serotonin (5-HT) depletion prevented the potentiating effect of BLS on the antidepressant response. These results show that improved behavioral outcome produced by BLS requires habenular astroglia and 5-HT tone as crucial buffer systems. Overall design: PFC mRNA profiles of 10-weeks-old naïve, stressed, and Ketamine + Scopolamine + light treated wild type mice were generated by deep sequencing, in duplicate, using Illumina.

抑郁症的有效治疗仍存在较大挑战。近期研究表明，亮光刺激（Bright Light Stimulation, BLS）对非季节性抑郁症具有确切疗效，但其具体作用机制仍不明晰。本研究构建了一种对包括氯胺酮在内的多种抗抑郁药均耐受的新型抑郁症小鼠模型，利用该模型证实：外侧缰核（lateral habenula, LHb）星形胶质细胞的化学遗传学激活，以及5-羟色胺（serotonin, 5-HT）耗竭，均会阻断亮光刺激对抗抑郁应答的增强效应。上述结果表明，亮光刺激所带来的行为学结局改善，依赖于缰核星形胶质细胞与5-羟色胺张力这两个关键的缓冲系统。实验设计：采用Illumina测序平台，通过深度测序获取10周龄野生型小鼠的前额叶皮层（prefrontal cortex, PFC）mRNA转录组谱，所有样本均设置双生物学重复。受试小鼠分为三组：未处理组、应激造模组，以及经氯胺酮、东莨菪碱联合亮光刺激处理组。