气体信号分子硫化氢调控海马BDNF/TrkB通路-神经发生拮抗慢性应激性抑郁

抑郁症的危害性大，从新的视角探讨其发生机制和防治靶点具有重要意义。H2S是一种新颖的气体性神经调质，基于文献和前期研究，我们认为抑郁与低水平的内源性H2S密切相关，H2S可通过调制海马BDNF/TrkB通路及神经发生拮抗抑郁。我们已发现H2S对急性应激性抑郁具有拮抗作用，在此基础上，本项目拟进一步建立慢性社交失败应激或慢性非预期温和应激等慢性应激性抑郁模型，观察慢性抑郁状态时内源性H2S生成及其生成体系的变化情况，探讨增加脑内H2S水平对慢性应激性抑郁的拮抗作用以及降低脑内H2S水平对慢性应激性抑郁的促进作用，以揭示内源性H2S与抑郁的关系和阐明H2S的抗抑郁作用；探讨H2S对海马BDNF/TrkB通路和神经发生的调控作用，从海马BDNF/TrkB通路-神经发生的角度揭示H2S抗抑郁的神经分子机制。本项目的开展有望从气体信号分子H2S这一新视角揭示抑郁的新机制，为其防治提供新靶点和策略。

Depression causes a great harm to our mental health. It is of great significance from a new perspective to explore the mechanisms and the targets for the prevention of depression. H2S is a novel gas-neuromodulator. Based on the literatures and our previous studies, we believe that the low level of endogenous H2S is closely related to depression and H2S can prevent depression by modulating hippocampal BDNF/TrkB pathway and neurogenesis. Based on our previous findings that H2S induces antidepressant-like effect in acute stress-induced depression, we will further reveal the relationship between endogenous H2S and depression and clarify the antidepressant effects of H2S using the model of chronic social defeat stress or chronic unpredictable mild stress by exploring the changs of endogenous H2S generation and its generation system, observing the antidepressant-like effect of enhancing the level of H2S in brain on chronic depression, and analyzing the role of decreasing the level of endogenous H2S in brain in promoting chronic depression.We will clarify the molecular mechanism of the antidepressant effect of H2S through exploring the role of BDNF/TrkB pathway and hippocampal neurogenesis in the antidepressant effect of H2S. Thus, the present work will reveal a novel mechanism of depression and provide novel targets and avenues for the treatment of depressive disorders from the new perspective of the gasotransmitters H2S.