Characterization of leptin's antidepressant activity

描述(申请人提供)：抑郁症是最常见的精神疾病之一。然而，抑郁症的发病机制和潜在的神经生物学仍然知之甚少，而且并不是所有的抑郁症患者对目前可用的治疗方法都有反应。我们最近的研究已经确定了瘦素在情绪过程中的作用，瘦素是一种从脂肪组织中分泌的激素，并证明了瘦素具有作为一种新型抗抑郁药物的潜力。该项目的目标是阐明瘦素抗抑郁药样作用的神经机制。首先，我们计划研究瘦素在海马神经发生中的潜在作用。其次，瘦素在海马体中的作用在情绪行为中的重要性将通过药理学和遗传学的方法来解决。第三，我们将研究瘦素和5-羟色胺能系统之间的功能相互作用。我们的主要假设是，瘦素的抗抑郁活性是由特定的大脑回路和神经递质介导的。这些研究将有助于从机制上理解瘦素在抑郁症中的作用，并为抑郁症的治疗提供新的治疗方法。

DESCRIPTION (provided by applicant): Depression is one of the most common mental illnesses. However, the pathogenesis and underlying neurobiology of depression remain poorly understood and not all depressed patients respond to current available treatments. Our recent studies have identified a role for leptin a hormone secreted from adipose tissue, in emotional processes and demonstrated that leptin has the potential as a novel antidepressant. The goal of this project is to elucidate the neural mechanisms underlying the antidepressant-like effects of leptin. First, we plan to investigate the potential role of leptin in hippocampal neurogenesis. Second, the importance of leptin action on the hippocampus in emotional behaviors will be addressed using both pharmacological and genetic approaches. Third, we will investigate the functional interaction between leptin and the serotonergic system. Our main hypothesis is that leptin's antidepressant-like activity is mediated by specific brain circuits and neurotransmitters. These studies will contribute to mechanistic understanding of the role of leptin in depression and provide insights into novel therapeutic approaches for the treatment of depressive disorders.