School of Biomedical Sciences & Pharmacy, The University of Newcastle, University Drive, Callaghan, NSW 2308, Australia.
Brain Behav Immun. 2010 Oct;24(7):1058-68. doi: 10.1016/j.bbi.2010.02.001. Epub 2010 Feb 11.
The current study, in parallel experiments, evaluated the impact of chronic psychological stress on physiological and behavioural measures, and on the activation status of microglia in 15 stress-responsive brain regions. Rats were subjected, for 14 days, to two 30 min sessions of restraint per day, applied at random times each day. In one experiment the effects of stress on sucrose preference, weight gain, core body temperature, and struggling behaviour during restraint, were determined. In the second experiment we used immunohistochemistry to investigate stress-induced changes in ionized calcium-binding adaptor molecule-1 (Iba1), a marker constitutively expressed by microglia, and major histocompatibility complex-II (MHC-II), a marker often expressed on activated microglia, in a total of 15 stress-responsive nuclei. We also investigated cellular proliferation in these regions using Ki67 immunolabelling, to check for the possibility of microglial proliferation. Collectively, the results we obtained showed that chronic stress induced a significant increase in anhedonia, a decrease in weight gain across the entire observation period, a significant elevation in core body temperature during restraint, and a progressive decrease in struggling behaviour within and over sessions. With regard to microglial activation, chronic stress induced a significant increase in the density of Iba1 immunolabelling (nine of 15 regions) and the number of Iba1-positive cells (eight of 15 regions). Within the regions that exhibited an increased number of Iba1-positive cells after chronic stress, we found no evidence of a between group difference in the number of MHC-II or Ki67 positive cells. In summary, these results clearly demonstrate that chronic stress selectively increases the number of microglia in certain stress-sensitive brain regions, and also causes a marked transition of microglia from a ramified-resting state to a non-resting state. These findings are consistent with the view that microglial activation could play an important role in controlling and/or adapting to stress.
当前的研究在平行实验中评估了慢性心理应激对生理和行为测量以及 15 个应激反应脑区中小胶质细胞激活状态的影响。大鼠每天接受两次 30 分钟的束缚，每天随机进行。在一项实验中，研究了应激对蔗糖偏好、体重增加、核心体温和束缚期间挣扎行为的影响。在第二项实验中，我们使用免疫组织化学方法研究了应激诱导的离子钙结合衔接分子-1（Iba1）变化，Iba1 是小胶质细胞组成性表达的标志物，主要组织相容性复合体-II（MHC-II）是激活的小胶质细胞上常见的标志物，共研究了 15 个应激反应核。我们还使用 Ki67 免疫标记研究了这些区域的细胞增殖，以检查小胶质细胞增殖的可能性。总的来说，我们的研究结果表明，慢性应激会导致快感缺失显著增加，整个观察期内体重增加减少，束缚期间核心体温显著升高，束缚内和束缚间挣扎行为逐渐减少。关于小胶质细胞激活，慢性应激会导致 Iba1 免疫标记密度（15 个区域中的 9 个）和 Iba1 阳性细胞数（15 个区域中的 8 个）显著增加。在慢性应激后 Iba1 阳性细胞数量增加的区域中，我们没有发现 MHC-II 或 Ki67 阳性细胞数量在组间存在差异的证据。总之，这些结果清楚地表明，慢性应激选择性地增加了某些应激敏感脑区中小胶质细胞的数量，并导致小胶质细胞从分支静止状态向非静止状态发生明显转变。这些发现与小胶质细胞激活可能在控制和/或适应应激中发挥重要作用的观点一致。
