Department of Anesthesiology, Women's Hospital of Nanjing Medical University, Nanjing Maternity and Child Health Care Hospital, Nanjing, China.
Department of Anesthesiology, Jinling Hospital, School of Medicine, Nanjing University, Nanjing, China.
Brain Res Bull. 2021 Jun;171:172-182. doi: 10.1016/j.brainresbull.2021.03.012. Epub 2021 Mar 19.
Both environmental stress and immune challenge can induce abnormal neurobehavior. However, the impact of chronic stress on immune challenge-related neurobehavioral abnormalities is still controversial. Hence, we aimed to investigate the effects of chronic stress on immune challenge-related neurobehavioral abnormalities and explore the possible underlying mechanisms. During the first set of experiments, mice were reared under normal condition (NC) or chronic stress (CS) for 4 consecutive weeks. They were allocated to the following four groups: NC + normal saline (NS) group, CS + NS group, NC + lipopolysaccharide (LPS) group, and CS + LPS group. Open field, elevated plus maze, fear conditioning, novel object recognition, and forced swimming tests were performed, and their tissues were harvested. During the second set of experiments, after rearing the mice under the above conditions for 3 weeks, microelectrodes were implanted into the CA1 of the hippocampus. After recovery for 1 week under the respective environmental conditions, the mice were allocated to four groups, as in the first experiments. The basal (home cage) and task (fear conditioning)-related local field potential (LFP) were recorded. In the present study, LPS significantly induced a decrease in the freezing to context and discrimination ratio. However, only the freezing to context was further reduced by prior chronic stress. This suggested that chronic stress worsened fear memory impairment induced by acute LPS challenge. Consistent with the change in fear memory, LPS significantly decreased the expression of PV in the CA1, which was further downregulated by prior chronic stress. On the other hand, LPS inhibited the power of both basal and task-related θ oscillations in the CA1. Only the task-related θ power was further decreased by chronic stress. In conclusion, our study showed that the phenotypic loss of PV interneurons and the decrease in the power of the θ oscillation in the CA1 aggravated by chronic stress may mediate, at least in part, the deterioration of fear memory impairment induced by LPS.
环境应激和免疫挑战均可导致异常的神经行为。然而，慢性应激对免疫挑战相关神经行为异常的影响仍存在争议。因此，我们旨在研究慢性应激对免疫挑战相关神经行为异常的影响，并探讨其可能的潜在机制。
在第一组实验中，将小鼠在正常条件（NC）或慢性应激（CS）下饲养 4 周。将它们分为以下四组：NC+生理盐水（NS）组、CS+NS 组、NC+脂多糖（LPS）组和 CS+LPS 组。进行了旷场实验、高架十字迷宫实验、恐惧条件反射实验、新物体识别实验和强迫游泳实验，并采集了它们的组织。
在第二组实验中，在上述条件下饲养小鼠 3 周后，将微电极植入海马 CA1 区。在各自的环境条件下恢复 1 周后，将小鼠分为与第一组实验相同的四组。记录基础（笼内）和任务（恐惧条件反射）相关的局部场电位（LFP）。
在本研究中，LPS 显著诱导了对上下文的冻结和辨别率的降低。然而，只有慢性应激后进一步降低了对上下文的冻结。这表明慢性应激加重了急性 LPS 挑战引起的恐惧记忆障碍。与恐惧记忆的变化一致，LPS 显著降低了 CA1 中 PV 的表达，而慢性应激进一步下调了 CA1 中 PV 的表达。另一方面，LPS 抑制了 CA1 中基础和任务相关θ振荡的功率。只有慢性应激进一步降低了与任务相关的θ功率。
总之，我们的研究表明，CA1 中 PV 中间神经元的表型丧失和θ振荡功率的降低，至少部分介导了 LPS 诱导的恐惧记忆障碍的恶化。
