Sepsis promotes gliogenesis and depletes the pool of radial glia like stem cells in the hippocampus
Sepsis promotes gliogenesis and depletes the pool of radial glia like stem cells in the hippocampus
复制标题
DOI：
10.1016/j.expneurol.2020.113591
复制
发表时间：
2021-01-25
影响因子：
5.3
通讯作者：
Kunze, Albrecht
中科院分区：
文献类型：
--
作者：
Bluemel, Priscilla;Wickel, Jonathan;Kunze, Albrecht
脓毒症相关脑病（SAE）是脓毒症幸存者的主要并发症，患病率高达 70%。尽管 SAE 的初始病理生理事件被认为发生在脓毒症的急性期，但越来越多的证据表明 SAE 会导致持续性脑功能障碍，并在以后的生活中导致严重的认知能力下降。先前的研究表明，海马结构特别参与导致后期萎缩。因此，人们对潜在的细胞机制知之甚少。在这里，我们假设败血症后海马的内源性神经干细胞和成体神经发生受到损害，并且当动物身体完全康复时，这些变化可能会导致持续的认知功能障碍。我们使用腹膜污染和感染 (PCI) 的小鼠脓毒症模型，并将前体细胞的不同标记方法与共聚焦显微镜研究相结合，以评估脓毒症后 42 天齿状体中的神经源性生态位。我们发现脓毒症后 i) 胶质细胞生成增加，ii) 被认为是假定的干细胞的放射状胶质细胞样细胞（1 型细胞）的绝对数量显着减少，iii) 新神经元的生成没有显着改变，而 iv) 新神经元的突触棘成熟受到损害，转向表达更不成熟和不太成熟的棘。总之，脓毒症主要导致 神经干细胞库的耗竭和齿状回的胶质生成增强，这表明由于脓毒症而导致海马体加速老化。
Sepsis associated encephalopathy (SAE) is a major complication of patients surviving sepsis with a prevalence up to 70%. Although the initial pathophysiological events of SAE are considered to arise during the acute phase of sepsis, there is increasing evidence that SAE leads to persistent brain dysfunction with severe cognitive decline in later life. Previous studies suggest that the hippocampal formation is particularly involved leading to atrophy in later stages. Thereby, the underlying cellular mechanisms are only poorly understood. Here, we hypothesized that endogenous neural stems cells and adult neurogenesis in the hippocampus are impaired following sepsis and that these changes may contribute to persistent cognitive dysfunction when the animals have physically fully recovered. We used the murine sepsis model of peritoneal contamination and infection (PCI) and combined different labeling methods of precursor cells with confocal microscopy studies to assess the neurogenic niche in the dentate gyms at day 42 postsepsis. We found that following sepsis i) gliogenesis is increased, ii) the absolute number of radial glia-like cells (type 1 cells), which are considered the putative stem cells, is significantly reduced, iii) the generation of new neurons is not significantly altered, while iv) the synaptic spine maturation of new neurons is impaired with a shift to expression of more immature and less mature spines.In conclusion, sepsis mainly leads to depletion of the neural stem cell pool and enhanced gliogenesis in the dentate gyrus which points towards an accelerated aging of the hippocampus due to septic insult.