Neural Basis of Light-dependent Depression and Anxiety

季节性情感障碍（SAD）是一种严重的抑郁症，影响数百万美国人， 在冬季反复出现抑郁和焦虑症状。经验证据表明， 抑郁症发作是由冬季光照不足引起的，但是 环境照明条件导致情感状态的波动仍然在很大程度上是未知的。中的这一空白 知识对于成功地识别风险因素和生物诊断提出了重要问题 SAD的标志物，以及开发更有效的治疗策略。其长期目标是 研究的目的是了解调节光线对情绪和焦虑影响的大脑机制。的 这项工作的目的是确定中枢食欲素能通路在介导光- 情感状态的依赖性波动拟议的工作将利用昼行草鼠（Arvichantis niloticus），这是PI组最近开发的SAD动物模型。有实质性的差异 夜间和白天的物种之间的昼夜节律和中央对光的反应。因此，我们认为， 一个昼夜模式对于阐明关键的基本机制至关重要 人的悲哀。在这个提议中要检验的中心假设是光调节情绪 通过作用于含有神经肽食欲素的大脑通路来缓解焦虑。采用草鼠模型， SAD，建议的工作包括三个具体目标：1）确定光对食欲素及其 2）为了验证强光刺激SAD大鼠神经元受体的假说， 通过增强日间草鼠的食欲素能通路，抑制抑郁和焦虑样行为， 3)确定食欲素能通路在缓解抑郁和焦虑样 行为，重点是5-HTergic背缝。该项目是创新的，因为它利用了一本小说， 昼夜动物模型和包括尖端分子生物学技术的多方法方法， AAV-shRNA，以验证食欲素能系统介导光对情绪影响的新假设 和焦虑这项拟议中的工作意义重大，因为它有望推进和扩大理解 环境照明条件的变化如何产生情绪和焦虑的波动， 有可能转化为更好地理解人类SAD的神经病理学基础。 最终，这些知识将有助于开发新的预防和治疗策略 治疗SAD和其他情绪障碍

Seasonal affective disorder (SAD) is a major depressive disorder affecting millions of Americans, who suffer recurring symptoms of depression and anxiety in the winter. Empirical evidence suggests that the depressive episodes are caused by insufficient light exposure during the winter months, but how changes in environmental lighting conditions lead to fluctuations in affective state remains largely unknown. This gap in knowledge presents an important problem for successfully identifying risk factors and biological diagnostic markers for SAD, as well as for developing more effective therapeutic strategies. The long-term goal of this research is to understand the brain mechanisms mediating the effects of light on mood and anxiety. The objective of the proposed work is to identify the role of central orexinergic pathways in mediating light- dependent fluctuations in affective state. The proposed work will utilize the diurnal grass rat (Arvichantis niloticus), an animal model of SAD recently developed in the PI's group. There are substantial differences between nocturnal and diurnal species in their circadian rhythms and central responses to light. Therefore, a diurnal model is of crucial importance for elucidating the fundamental mechanisms critically underlying SAD in the diurnal human. The central hypothesis to be tested in this proposal is that light regulates mood and anxiety by acting on brain pathways containing the neuropeptide, orexin. Using the grass rat model of SAD, the proposed work contains three Specific Aims: 1) To determine the effects of light on orexin and its receptors in the diurnal grass rat model of SAD, 2) To test the hypothesis that bright light alleviates depression- and anxiety-like behaviors via enhancing the orexinergic pathways in the diurnal grass rats, and 3) To identify the downstream targets of orexinergic pathways in alleviating depression- and anxiety-like behaviors with a focus on the 5-HTergic dorsal raphe. The project is innovative because it utilizes a novel diurnal animal model and a multi-method approach including cutting-edge molecular biology techniques i.e. AAV-shRNA, to test a novel hypothesis that the orexinergic system mediates the effects of light on mood and anxiety. The proposed work is significant because it is expected to advance and expand understanding of how changes in environmental lighting conditions produce fluctuations in mood and anxiety, which has the potential to translate into better understanding of the neuropathology underlying SAD in humans. Ultimately, such knowledge will contribute to the development of novel preventive and therapeutic strategies for SAD and other mood disorders.