Delcourte Sarah, Bouloufa Amel, Rovera Renaud, Brunet Elie, Le Hiep D, Williams April E, Panda Satchidananda, Azmani Rihab, Raineteau Olivier, Dkhissi-Benyahya Ouria, Haddjeri Nasser
Univ Lyon, Université Claude Bernard Lyon 1, Inserm U1208, Stem Cell and Brain Research Institute, Bron, France.
Regulatory Biology Laboratory, Salk Institute for Biological Studies, La Jolla, CA, United States.
Front Pharmacol. 2025 Apr 23;16:1592909. doi: 10.3389/fphar.2025.1592909. eCollection 2025.
Beside image vision, light plays a pivotal role in regulating diverse non-visual functions, including affective behaviors. Recently, bright light stimulation (BLS) was revealed to be beneficial for treating non-seasonal depression, although its mechanism of action is not fully understood.
We developed a novel mouse model of refractory depression, induced through social isolation and chronic despair during the active (dark) phase of the animal, and we have tested if antidepressant treatments, including BLS, could protect against anxio-depressive-like behavior.
We report that anxiety- and depressive-like behaviors are resistant to BLS as well as to both conventional and new antidepressants, including ketamine. Remarkably, we unveil that BLS potentiates the effect of antidepressants, and this beneficial effect is mediated via rod retinal photoreceptors. Furthermore, we demonstrate that both chemogenetic activation of lateral habenula (LHb) astroglia and serotonin (5-HT) depletion prevent the potentiating effect of BLS on chronic despair.
These results reveal, for the first time, that BLS enhances the efficacy of antidepressants through an unexpectedly circuit involving rods, LHb astroglia and 5-HT.
除了视觉成像外，光在调节多种非视觉功能（包括情感行为）中起着关键作用。最近，强光刺激（BLS）被发现对治疗非季节性抑郁症有益，尽管其作用机制尚未完全明确。
我们通过在动物活动（黑暗）阶段进行社会隔离和慢性绝望诱导，建立了一种新型的难治性抑郁症小鼠模型，并测试了包括BLS在内的抗抑郁治疗是否能预防类似焦虑抑郁的行为。
我们报告称，类似焦虑和抑郁的行为对BLS以及传统和新型抗抑郁药（包括氯胺酮）均有抗性。值得注意的是，我们发现BLS可增强抗抑郁药的效果，且这种有益效果是通过视杆视网膜光感受器介导的。此外，我们证明，外侧缰核（LHb）星形胶质细胞的化学遗传激活和血清素（5-HT）耗竭均可阻止BLS对慢性绝望的增强作用。
这些结果首次揭示，BLS通过一个意外的回路增强抗抑郁药的疗效，该回路涉及视杆细胞、LHb星形胶质细胞和5-HT。
