Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation
Stress-induced elevation of glucocorticoids increases microglia proliferation through NMDA receptor activation
复制标题
DOI：
10.1016/j.jneuroim.2005.09.012
复制
发表时间：
2006-02-01
影响因子：
3.3
通讯作者：
Bonneau, RH
中科院分区：
文献类型：
--
作者：
Nair, A;Bonneau, RH
糖皮质激素的免疫抑制特性已经在体外和体内得到了很好的证明。这种糖皮质激素介导的免疫抑制也在中枢神经系统(CNS)内的免疫细胞中观察到。例如，小胶质细胞在体外用糖皮质激素治疗时表现出增殖减少、细胞因子产生和抗原呈递减少。尽管有这些体外发现，糖皮质激素对体内小胶质细胞功能的影响还没有得到充分的研究。为了确定中枢神经系统内糖皮质激素和小胶质细胞之间的相互作用，我们使用了心理应激的约束模型来提高小鼠的皮质酮水平。对应激小鼠小胶质细胞的定量检测表明，四次应激诱导了小胶质细胞的增殖。这种增殖是皮质酮诱导中枢神经系统内N-甲基-D-天冬氨酸(NMDA)受体激活的功能，因为皮质酮合成、糖皮质激素受体或NMDA受体的阻断都阻止了应激诱导的小胶质细胞数量的增加。此外，NMDA受体拮抗剂MK-801阻止了非应激小鼠服用外源性皮质酮后小胶质细胞的增加。我们得出结论，NMDA受体的激活和随后的小胶质细胞增殖是皮质酮水平升高的下游效应。这些发现表明，糖皮质激素水平的升高能够激活体内的小胶质细胞，并表明应激能够在中枢神经系统内诱导促炎反应。促炎症的小胶质细胞反应可能是导致中枢神经系统各种应激性炎症状态发生的因素之一。(C)2005 Elsevier B.V.保留所有权利。
The immunosuppressive nature of glucocorticoids has been well documented both in vitro and in vivo. This glucocorticoid-mediated immunosuppression has also been observed in immune cells within the central nervous system (CNS). For example, microglia have previously been shown to exhibit decreased proliferation, cytokine production, and antigen presentation upon treatment with glucocorticoids in vitro. Despite these in vitro findings, the impact of glucocorticoids on microglia function in vivo has not been fully investigated. To determine the interaction between glucocorticoids and microglia within the CNS, we used a restraint model of psychological stress to elevate corticosterone levels in mice. Quantification of microglia from stressed mice indicated that four sessions of stress induced the proliferation of microglia. This proliferation was a function of corticosterone-induced activation of the N-methyl-D-aspartate (NMDA) receptor within the CNS since blockade of corticosterone synthesis, the glucocorticoid receptor, or the NMDA receptor each prevented stress-induced increases in microglia number. In addition, the NMDA receptor antagonist MK-801 prevented increases in microglia following exogenous corticosterone administration to non-stressed mice. We conclude that activation of the NMDA receptor and subsequent microglia proliferation is a downstream effect of elevated corticosterone levels. These findings demonstrate that elevated levels of glucocorticoids are able to activate microglia in vivo and suggest that stress is able to induce a pro-inflammatory response within the CNS. A pro-inflammatory microglia response may be a contributing factor in the development of various stress-induced inflammatory conditions in the CNS. (c) 2005 Elsevier B.V. All rights reserved.