抑郁症的发病机理有多种假说。目前较为前瞻和具有潜力的是"炎性与神经退化假说"。认为抑郁症与炎性免疫和神经发生的抑制有关。我们前期研究表明中枢和外周炎性细胞因子的激活均能诱导抑郁行为，但外周炎性免疫诱导的抑郁行为其时程效应很短，中枢炎性免疫诱发的抑郁行为时程较长。且脑内施予抗炎性细胞因子能逆转抑郁行为。这些发现表明脑内炎性反应是致抑郁症的关键因素。但脑内炎性免疫致抑郁症的机理迄今尚未清楚地阐释。为弄清炎性所致的抑郁行为是否与由炎性引起的神经发生的抑制有关，本项目采用中枢炎性免疫应答造模，系统地探讨炎性细胞因子调控抑郁行为与海马神经发生的关系。分别从抑郁行为的变化时程、促神经发生干预、抗炎性免疫干预、神经发生的阻断等多途径探讨炎性免疫对抑郁行为的调控及与神经发生活动的关系。相信该研究会在揭示抑郁障碍机制上有丰富的洞见和新的突破，并有望为抑郁症的预防和治疗带来新的靶标和策略。

There are many theories on the mechanism of the etiology of depression. The current one is the inflammatory & neurodegenerative hypothesis of depression, which considers that inflammatory and neurodegenerative processes play an important role in depression. Our previous work demonstrated that both central and peripheral pro-inflammatory challenges could induce depressive-like behaviors in rats. However, while depressive-like behaviors induced by peripheral way last only a few hours, the central pro-inflammatory challenges induced significant long lasting depressive-like behaviors. It was also demonstrated that the anti-inflammatory cytokine IL-10 reversed depressive-like behavior induced by forced swim stress. These results indicate that the central inflammatory process play critical role in the development of depression. However, whether the depressive behavior induced by pro-inflammatory challenges is involved in the mechanism of neurogenesis has not known. The present project attempts to investigate the relationship between the depressive-like behavior induced by pro-inflammatory challenges and the neurodegenerative processes in the hippocampus. By using a central inflammation model of depression and multiple interventions, such as anti-inflammatory cytokine IL-10 treatment, exogenous FGF treatment, and blocking FGF-ERK pathway, the role of neurogenesis in depressive-like behaviors and the interactions between the behaviors , cytokines, and neurogenesis were investigated. This research project may provide new insights into the mechanism of the depression induced by inflammatory cytokines as well as the new target and treatment approach for the clinical depression therapy.

目前抑郁症的“细胞因子假说"发展为“炎性与神经退化假说"。认为抑郁症与炎性免疫和神经发生的抑制有关。 但神经发生的抑制在炎性免疫所致抑郁症中扮演什么角色，至今尚不清楚。本项目采用中枢炎性免疫应答造模，系统地探讨炎性细胞因子调控抑郁行为与脑内成体神经发生的关系。主要发现：1、中枢炎性免疫激活引起了明显的抑郁行为，同时抑制成体神经发生。在海马颗粒细胞下层、内侧前额叶以及内侧缰核均观察到细胞增殖的抑制。2、海马神经元的增殖和新生神经元的成活（BrdU 阳性细胞数）和不成熟细胞的数目（DCX 阳性细胞数）均与抑郁行为的各项指标包括糖水偏好，旷场中行进距离，悬尾不动时间，新奇抑制摄食进食潜伏期都密切相关。