抑郁症是一种常见精神障碍，严重威胁人类健康。应激与遗传易损性是导致抑郁症发病的主要原因，海马对应激最敏感，应激导致海马神经发生下降是抑郁症的特征。甘丙肽(Gal)为含有29/30个氨基酸的神经肽，通过三种G蛋白偶联受体发挥多种生物学效应。研究发现GalR mRNA在神经发生相关的齿状回颗粒下区表达，表明Gal可能参与神经发生。本研究组前期发现Gal阳性神经元主要分布于海马齿状回,且将Gal海马局部注射发现BrdU阳性神经元增加,但Gal能否通过影响海马神经发生改善抑郁症状尚不得而知。为此，本项目拟观察Gal是否表达于神经元发生至成熟的各阶段及其对神经发生的影响；原代培养海马神经干细胞，探讨Gal影响神经发生的信号转导通路；建立慢性不可预见性应激模型，观察抑郁状态下齿状回Gal及其受体的表达变化及神经发生情况，进而明确Gal在海马神经发生中的作用机制，为临床抗抑郁治疗提供新的靶点和方向。

Depression is a high prevalence mental disorder which severely threats human health. Stress and genetic vulnerability are the main reasons leading to the onset of depression. In CNS, hippocampal neurons are most sensitive to stress, and stress induced hippocampal neurogenesis failure is an important feature of depression. Containing 29/30 amino acid neuropeptide galanin (Galanin,Gal) is widely distributed in the peripheral and central nervous system and plays a variety of biological effects through three G protein-coupled receptors (GalR1-3) .Recent studies have shown that in the adult mammalian hippocampus dentate gyrus granular layer, GalR mRNA expression is detected. This zone is well known as related with neurogenesis which infers Gal may be involved in neurogenesis in hippocampus. It's been found in our former studies that positive galanin neurons are mainly distributed in dentate gyrus and microinjection of galanin in this zone could induce increased BrdU staining which represented neurogenesis. However, it is still unknown whether depressive symptoms can be improved through Gal induced hippocampal neurogenesis. In this project, Gal expression pattern in every developmental stage in dentate gyrus will be examined in order to find out how it affects neurogenesis. At the meantime, through primary cultured hippocampal neural stem cells, we will eliminate signal transduction pathways concerning Gal induced neurogenesis. Taking the advantage of chronic unpredicted stress model, we intend to observe Gal receptor expression change and neuronal cell proliferation in dentate gyrus,and clarify the underlying mechanism of Gal's fuctions in hippocampal neural regeneration in depressive state.This project will provide new sights and direction in clinical antidepressant treatment.