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.

中文翻译：

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一种不同于SSRI诱导的抗抑郁作用的新型5HT3受体-IGF1机制。

抑郁症是一种常见的精神障碍，全世界约有3.5亿人受到影响。尽管选择性5-羟色胺再摄取抑制剂（SSRIs）是使用最广泛的抗抑郁药，但相当一部分抑郁症患者无法通过SSRIs缓解。在这项研究中，我们表明3型血清素受体（5HT3R）激动剂可诱导抗抑郁作用以及独立于氟西汀（一种常用的SSRI）的海马神经发生。值得注意的是，我们的组织学分析表明，5HT3R和胰岛素样生长因子1（IGF1）在海马齿状回的亚颗粒区的同一神经元中表达。此外，我们的体内微透析分析显示5HT3R调节海马细胞外IGF1水平，并且我们还显示5HT3R依赖性海马神经发生是由IGF1水平升高介导的。