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。应激对小胶质细胞激活的影响分别在未应激、抑制1 h和2 h后以及应激2 h后释放6 h时进行评估。在控制条件下，静息小胶质细胞以其小体和长而细的突起为特征分布在整个大脑中。应激后，小胶质细胞的形态激活遍及整个大脑，包括丘脑、下丘脑、海马、第三脑室周围的黑质和中央灰质。应激6小时后，形态激活虽减弱，但仍存在。有趣的是，在第三脑室附近，显著的小胶质细胞激活更为明显。应激激活的小胶质细胞对ED1和OX-6无免疫反应，提示应激激活的小胶质细胞不参与吞噬活性。此外，我们还测量了作为小胶质细胞功能性炎症标志物的IL-lb、IL-6和iNOS的水平。结果表明，这些非炎症标志物的水平在应激期间和应激后没有改变，表明炎症可能不伴有应激诱导的小胶质细胞激活。接下来，为了研究白细胞介素-18的作用，我们在腹腔内注射重组IL-18。结果清楚地表明，IL-18注射后，形态学上的小胶质细胞被激活。此外，我们比较了野生型和IL-18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敲除小鼠中，应激诱导的小胶质细胞激活并没有完全消除，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。综上所述，急性应激不会引起大脑的炎症反应。因此，急性应激本身不太可能引起由小胶质细胞炎症引起的神经元损伤。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