海马CA3锤体神经元Galectin-3调控海马突触可塑性发挥抗抑郁作用的机制研究

海马突触可塑性下降和突触丢失是抑郁症发生发展的神经生物学基础，发掘增强突触可塑性的潜在靶点是近年来研究及治疗抑郁症的新方向。我们的前期研究发现，抑郁症患者血清半乳糖凝集素-3（Gal-3）下调；海马CA3锤体神经元Gal-3可能参与抑郁症的发病过程。据此，本项目提出假说：海马CA3锤体神经元Gal-3通过Akt-CREB-BDNF通路促进神经再生；增加胞内Ca2+浓度，增强海马突触可塑性；亦可通过CA3-DLS神经元轴突投射调节抑郁行为。本研究以基因过表达或基因敲减海马CA3锤体神经元Gal-3，从正反两方面研究Gal-3在抑郁行为、海马突触可塑性调控中的作用及其机制，使用Gal-3及其拮抗剂进一步确证。从多层面证明海马CA3锤体神经元Gal-3是治疗抑郁症的潜在靶点。

The impaired hippocampal synaptic plasticity and the loss of synapses are the neurobiological basis for the development of depression. Exploring the new molecular target for enhancing synaptic plasticity is the new strategy on study and therapy of depression. Our previous studies have found that serum galectin-3 (Gal-3) is decreased in patients with depression and Gal-3 in hippocampal CA3 pyramidal neurons may be involved in the pathogenesis of depression. Accordingly, we hypothesize that Gal-3 in hippocampal CA3 pyramidal neurons promotes neurogenesis by activating Akt-CREB-BDNF pathway, increases intracellular concentration of Ca2+ to improve hippocampal synaptic plasticity and it can also modulate depressive behaviors via hippocampal CA3 pyramidal neurons afferent to dorsolateral septum. In this project, Gal-3 in hippocampal CA3 pyramidal neurons will be overexpressed or knocked down to study the role of Gal-3 in the regulation of depressive behavior and hippocampal synaptic plasticity and the underlying mechanisms from two aspects of positive and negative regulation and further confirmed by using Gal-3 and its antagonist. This study will prove from multiple angles that Gal-3 in hippocampal CA3 pyramidal neurons is a potential target for the treatment of depression.