A novel 5HT3 receptor-IGF1 mechanism distinct from SSRI-induced antidepressant effects
A novel 5HT3 receptor-IGF1 mechanism distinct from SSRI-induced antidepressant effects
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DOI：
10.1038/mp.2017.87
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发表时间：
2018-04-01
影响因子：
11
通讯作者：
Shimada, S.
中科院分区：
文献类型：
--
作者：
Kondo, M.;Koyama, Y.;Shimada, S.
抑郁症是一种常见的精神疾病，影响着全球约3.5亿人。虽然选择性5-羟色胺再摄取抑制剂（SSRIs）是最广泛使用的抗抑郁药，但仍有相当比例的抑郁症患者不能通过SSRIs达到缓解。在这项研究中，我们表明，5-羟色胺3型受体（5 HT 3R）激动剂诱导抗抑郁作用以及海马神经发生独立的氟西汀（一种常用的SSRI）。值得注意的是，我们的组织学分析表明，5-HT 3R和胰岛素样生长因子1（IGF 1）表达在相同的神经元在海马齿状回的颗粒下区。此外，我们的体内微透析分析表明，5 HT 3R调节海马细胞外IGF 1水平，我们还表明，5 HT 3R依赖的海马神经发生介导的IGF 1水平的增加。总而言之，我们的研究结果表明了一种新的5 HT 3R-IGF 1机制，该机制与氟西汀诱导的反应不同，并为抑郁症提供了一种新的治疗靶点，特别是为SSRI耐药的抑郁症患者带来了显着的益处。
Depression is a common mental disorder affecting around 350 million people worldwide. Although selective serotonin reuptake inhibitors (SSRIs) are the most widely used antidepressants, a significant proportion of depressed patients do not achieve remission with SSRIs. In this study, we show that a serotonin type 3 receptor (5HT3R) agonist induces antidepressant effects as well as hippocampal neurogenesis independent of fluoxetine (a commonly used SSRI). Notably, our histological analysis reveals that 5HT3R and insulin-like growth factor 1 (IGF1) are expressed in the same neurons in the subgranular zone of the hippocampal dentate gyrus. Furthermore, our in vivo microdialysis analysis shows that 5HT3R regulates hippocampal extracellular IGF1 levels, and we also show that 5HT3R-dependent hippocampal neurogenesis is mediated by increased IGF1 levels. Altogether, our findings suggest a novel 5HT3R-IGF1 mechanism that is distinct from fluoxetine-induced responses and that provides a new therapeutic target for depression, especially bringing significant benefits for SSRI-resistant depressed patients.