Blockade of Mineralocorticoid and Glucocorticoid Receptors Reverses Stress-Induced Motor Impairments
Blockade of Mineralocorticoid and Glucocorticoid Receptors Reverses Stress-Induced Motor Impairments
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DOI：
10.1159/000329988
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发表时间：
2011-01-01
影响因子：
4.1
通讯作者：
Metz, Gerlinde A.
中科院分区：
文献类型：
--
作者：
Jadavji, Nafisa M.;Supina, Rebecca D.;Metz, Gerlinde A.
目的：应激和糖皮质激素可影响运动能力和运动系统的病理变化。经典的观点认为糖皮质激素受体（GR）介导了大多数应激诱导的行为变化。然而，最近的研究结果认为盐皮质激素受体（MR）在调节行为中起着更重要的作用。本研究的目的是分离MR与GR激活在运动和应激相关运动中断中的影响。研究方法：测试各组雄性和雌性大鼠的熟练伸手和旷场行为，并分别经口给予MR和GR激动剂或拮抗剂。结果如下：选择性急性激活的MR（醛固酮）和GR（地塞米松）减少运动成功的幅度类似于应力诱导的损害在男性和女性动物。相比之下，拮抗剂治疗阻断MR（RU-28318）或GR（米非司酮，RU-486）预防急性束缚应激或皮质酮治疗引起的运动障碍。此外，这两种拮抗剂逆转慢性应激和糖皮质激素诱导的运动障碍的值与基线水平相当。治疗动物的成功率更高，同时肢体熟练运动的表现也有所改善。此外，MR和GR拮抗剂的联合治疗对目标和朝向达到目标的进展具有附加益处。结论：MR和GR对运动系统功能的影响具有部分协同作用。雄性和雌性对MR和GR激活或阻断的反应相当。在运动控制中需要平衡激活MR和GR，这需要在干预策略中加以考虑，以改善健康和疾病方面的表现。版权所有（C）2011 S. Karger AG，巴塞尔
Aim: Stress and glucocorticoids can influence movement performance and pathologies of the motor system. The classic notion assumes that the glucocorticoid receptor (GR) mediates the majority of stress-induced behavioral changes. Nevertheless, recent findings have attributed a more prominent role to the mineralocorticoid receptor (MR) in modulating behavior. The purpose of this study was to dissociate the impact of MR versus GR activation in movement and stress-associated motor disruption. Methods: Groups of male and female rats were tested in skilled reaching and open field behavior and treated peri-orally with either agonists or antagonists for MR and GR, respectively. Results: Selective acute activation of MR (aldosterone) and GR (dexamethasone) decreased movement success with a magnitude similar to stress-induced impairment in male and female animals. By contrast, antagonist treatment to block MR (RU-28318) or GR (Mifepristone, RU-486) prevented motor impairments caused by acute restraint stress or corticosterone treatment. Moreover, both antagonists reversed chronic stress-and glucocorticoid-induced motor impairments to values comparable to baseline levels. Higher success rates in treated animals were accompanied by improved performance of skilled limb movements. In addition, combined treatment with MR and GR antagonists had additive benefit on aim and advance towards the reaching target. Conclusion: These observations suggest that MR or GR equally influence motor system function with partially synergistic effects. Males and females show comparable responses to MR and GR activation or blockade. The need for balanced activation of MRs and GRs in motor control requires consideration in intervention strategies to improve performance in health and disease. Copyright (C) 2011 S. Karger AG, Basel