Tang Ming-Ming, Lin Wen-Juan, Pan Yu-Qin, Guan Xi-Ting, Li Ying-Cong
Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; University of Chinese Academy of Sciences, Beijing, China.
Key Laboratory of Mental Health, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China; Brain-Behavior Research Center, Institute of Psychology, Chinese Academy of Sciences, Beijing 100101, China.
Physiol Behav. 2016 Jul 1;161:166-173. doi: 10.1016/j.physbeh.2016.04.034. Epub 2016 Apr 19.
Our previous work found that triple central lipopolysaccharide (LPS) administration could induce depressive-like behaviors and increased central pro-inflammatory cytokines mRNA, hippocampal cytokine mRNA in particular. Since several neuroinflammation-associated conditions have been reported to impair neurogenesis, in this study, we further investigated whether the neuroinflammation induced depression would be associated with hippocampal neurogenesis dysfunction. An animal model of depression induced by triple central lipopolysaccharide (LPS) administration was used. In the hippocampus, the neuroinflammatory state evoked by LPS was marked by an increased production of pro-inflammatory cytokines, including interleukin-1β, interleukin-6, and tumor necrosis factor-α. It was found that rats in the neuroinflammatory state exhibited depressive-like behaviors, including reduced saccharin preference and locomotor activity as well as increased immobility time in the tail suspension test and latency to feed in the novelty suppressed feeding test. Adult hippocampal neurogenesis was concomitantly inhibited, including decreased cell proliferation and newborn cell survival. We also demonstrated that the decreased hippocampal neurogenesis in cell proliferation was significantly correlated with the depressive-like phenotypes of decreased saccharine preference and distance travelled, the core and characteristic symptoms of depression, under neuro inflammation state. These findings provide the first evidence that hippocampal neurogenesis dysfunction is correlated with neuroinflammation-induced depression, which suggests that hippocampal neurogenesis might be one of biological mechanisms underlying depression induced by neruoinflammation.
我们之前的研究发现，三次脑室内注射脂多糖（LPS）可诱发抑郁样行为，并增加中枢促炎细胞因子的mRNA表达，尤其是海马细胞因子的mRNA表达。由于已有报道称几种与神经炎症相关的疾病会损害神经发生，因此在本研究中，我们进一步探究神经炎症诱发的抑郁症是否与海马神经发生功能障碍有关。我们采用了三次脑室内注射脂多糖（LPS）诱发抑郁症的动物模型。在海马体中，LPS诱发的神经炎症状态表现为促炎细胞因子生成增加，包括白细胞介素-1β、白细胞介素-6和肿瘤坏死因子-α。结果发现，处于神经炎症状态的大鼠表现出抑郁样行为，包括糖精偏好降低、运动活动减少，以及在悬尾试验中不动时间增加和在新奇抑制摄食试验中摄食潜伏期延长。成年海马神经发生也随之受到抑制，包括细胞增殖减少和新生细胞存活减少。我们还证明，在神经炎症状态下，细胞增殖中海马神经发生的减少与糖精偏好降低和行进距离缩短等抑郁样表型显著相关，而糖精偏好降低和行进距离缩短是抑郁症的核心和特征性症状。这些发现首次证明海马神经发生功能障碍与神经炎症诱发的抑郁症相关，这表明海马神经发生可能是神经炎症诱发抑郁症的生物学机制之一。
