College of Life Science, Hebei Normal University, Shijiazhuang 050016, PR China.
Brain Res Bull. 2012 Aug 1;88(5):471-6. doi: 10.1016/j.brainresbull.2012.04.008. Epub 2012 Apr 17.
Previous research has indicated that chronic stress induces inflammatory responses, cognitive impairments, and changes in microglia and astrocytes. However, whether stress-induced changes following recovery are reversible is unclear. The present study examined the effects of chronic unpredictable stress (CUS) following recovery on spatial learning and memory impairments, changes in microglia and astrocytes, and interleukine-1β (IL-1β) and glial-derived neurotrophic factor (GDNF) levels. Mice were randomly divided into control, stress, and recovery groups, and CUS was applied to mice in the stress and recovery groups for 40 days. Following the application of CUS, the recovery group was allowed 40 days without stress. The results of the Morris water maze illustrated that CUS-induced spatial learning and memory impairments could be reversed or even improved by a period of recovery. Immunohistochemical tests revealed that CUS-induced alterations in microglia could dissipate with time in the CA3 region of the hippocampus and prelimbic areas. However, CUS-induced activation of astrocytes was sustained in the CA3 area following recovery. Western blot analyses revealed that CUS induced a significant increase of GDNF and a significant decrease in IL-1β. Additionally, increased GDNF levels were sustained in the hippocampus during recovery. In conclusion, this study provides evidence that CUS-induced learning and memory impairments could be reversible following recovery. However, activated astrocytes and increased GDNF levels in the hippocampus remained elevated after recovery, suggesting that activated astrocytes and increased GDNF play important roles in the adaptation of the brain to CUS and in repairing CUS-induced impairments during recovery.
先前的研究表明，慢性应激会引起炎症反应、认知障碍以及小胶质细胞和星形胶质细胞的变化。然而，应激后恢复时的变化是否可逆尚不清楚。本研究探讨了慢性不可预测应激（CUS）恢复后对空间学习和记忆障碍、小胶质细胞和星形胶质细胞变化以及白细胞介素-1β（IL-1β）和胶质细胞源性神经营养因子（GDNF）水平的影响。将小鼠随机分为对照组、应激组和恢复组，对应激组和恢复组的小鼠施加 40 天的 CUS。施加 CUS 后，恢复组可在 40 天内无应激。Morris 水迷宫的结果表明，通过一段时间的恢复，可以逆转或甚至改善 CUS 引起的空间学习和记忆障碍。免疫组织化学测试显示，海马 CA3 区和前扣带回区的小胶质细胞的 CUS 诱导的变化可以随时间消散。然而，恢复后 CA3 区的星形胶质细胞的激活仍持续存在。Western blot 分析显示，CUS 诱导 GDNF 显著增加，IL-1β显著减少。此外，恢复过程中海马中的 GDNF 水平持续增加。综上所述，本研究提供了证据表明，CUS 引起的学习和记忆障碍在恢复后可能是可逆的。然而，恢复后海马中的激活星形胶质细胞和增加的 GDNF 水平仍保持升高，这表明激活的星形胶质细胞和增加的 GDNF 在大脑适应 CUS 和修复 CUS 引起的损伤方面发挥着重要作用。
