Does stress promotes neurodegenerative changes?

本研究的目的是探讨心理/生理应激对小胶质细胞激活的影响。观察应激对小胶质细胞活化的影响，分别在非应激状态、束缚结合水浸应激后1h和2 h，以及应激解除后6 h观察应激对小胶质细胞活化的影响。在对照条件下，静息状态的小胶质细胞胞体较小，突起细长，分布于大脑各处。应激后，小胶质细胞在包括丘脑、下丘脑、海马体、黑质和围绕第三脑室的中央灰质在内的整个脑内都有形态上的激活。应激6小时后，形态激活虽然减弱，但仍存在。有趣的是，显著的小胶质细胞激活在第三脑室附近更为明显。应激激活的小胶质细胞不对ED1或OX-6免疫反应，提示应激激活的小胶质细胞不参与…吞噬功能增强。此外，我们还检测了小胶质细胞功能炎症标志物IL-1b、IL-6和iNOS水平。结果表明，在应激过程中和应激后，这些炎性标志物的水平没有改变，提示炎症可能不伴随应激诱导的小胶质细胞激活。接下来，为了研究IL-18的作用，我们将重组IL-18注射到腹膜腔内。结果清楚地表明，IL-18作用后出现了形态上的小胶质细胞激活。此外，我们还比较了野生型和IL-18基因敲除小鼠应激诱导的小胶质细胞激活。结果表明，与野生型小鼠相比，应激诱导的小胶质细胞激活明显减少。然而，在IL-18基因敲除的小鼠中，应激诱导的小胶质细胞激活并未完全消除，这表明任何其他因素都可能触发应激诱导的小胶质细胞激活。总而言之，急性应激不会在大脑中引发炎症反应。因此，急性应激本身不太可能导致由小胶质细胞炎症引起的神经元损伤。较少

The goal of the present study was to investigate the influence of psychological/physical stress on microglial activation. The effect of stress on microglial activation was evaluated in unstressed or after 1 h and 2 h of restraint combined with water immersion stress as well as 6 h after release from the 2 h of stress. Under control conditions, resting microglia characterized by their small somas and long and fine processes were distributed throughout the brain. Following the stress, morphological activation of microglia was observed throughout the brain including the thalamus, hypothalamus, and hippocampus, substantia nigra and central grey surround the 3rd ventricle. Six hours after the stress, morphological activation was still present although diminished. Intriguingly, significant microglial activation was more pronounced in the vicinity of the third ventricle. Stress-activated microglia was not immunoreactive to ED1 or OX-6, suggesting that stress-activated microglia are not involv … More ed in the phagocytic activity. In addition, we measured the levels of IL-lb, IL-6 and iNOS, as functional inflammatory markers of microglia. The result demonstrated that the levels of these ninflammatory markers did not alter during and after the stress, suggesting that inflammation may not be accompanied with the stress-induced microglial activation. Next, to investigate the effect of interleukin-18, we injected recombinant IL-18 in the intraperitoneal space. The result clearly demonstrated that morphological microglial activation occurred following IL-18 inejction. Furthermore, we compared stress-induced microglial activation between wild type and IL-18 knock out mice. The result demonstrated that stress-induced microglial activation was significantly reduced as compared to that of wild type mice. However, stress-induced microglial activation was not completely abolished in IL-18 knock out mice, suggesting that any other factors may trigger stress-induced microglial activation. As a summary, acute stress did not induce inflammatory reactions in the brain. Thus, it is less likely that acute stress, itself, may cause the neuronal damages that are caused by microglial inflammation. Less