Kumar Gaurav, Couper Abbie, O'Brien Terence J, Salzberg Michael R, Jones Nigel C, Rees Sandra M, Morris Margaret J
Department of Medicine, Royal Melbourne Hospital, University of Melbourne, Melbourne, Vic, Australia.
Psychoneuroendocrinology. 2007 Aug;32(7):834-42. doi: 10.1016/j.psyneuen.2007.05.011. Epub 2007 Jul 5.
We have previously demonstrated that low-dose corticosterone (CS) administration, used as a model of the effect of chronic stress, accelerates epileptogenesis in the electrical amygdala kindling rat model of temporal lobe epilepsy (TLE). This current study examined the relative contributions to this effect of mineralocorticoid (MR) and glucocorticoid (GR) subtypes of glucocorticoid receptors. Female non-epileptic wistar rats 10-13 weeks of age were implanted with a bipolar electrode into the left amygdala. Five treatment groups were subjected to rapid amygdala kindling: water-control (n=9), CS treated (6 mg/100 ml added to drinking water; n=9), CS+spironolactone (MR antagonist, 50 mg/kg sc; n=9), CS+mifepristone (GR antagonist, 25 mg/kg sc; n=9), and CS+both antagonists (n=7). Rats were injected with vehicle or the relevant antagonist twice daily for the entire kindling period. Experimental groups differed significantly in the number of stimulations required to reach the 'fully kindled state' (Racine, 1972) ANOVA, F(4,38)=2.73, p=0.04). Amygdala kindling was accelerated in the CS-treated group compared with water controls (mean stimulations for full kindling: 45.2 vs. 86.5, p<0.01). This acceleration was inhibited by both the MR and GR antagonist treatments (mean stimulations: 69.6 and 70.4, p=0.04 and 0.04 vs. CS group, respectively), with the kindling rates in these groups not significantly different from water-treated subjects (p=0.26 and 0.29, respectively). The kindling rates in the MR and GR antagonist treatment groups did not significantly differ from each other (p=0.93), nor from the combined treatment group (mean stimulations: 62.8, p=0.59 and 0.54, respectively). This study demonstrates that activation of both high-affinity (MR) and low-affinity (GR) glucocorticoid receptors are involved in mediating CS-induced acceleration of amygdala kindling epileptogenesis.
我们之前已经证明，低剂量皮质酮（CS）给药作为慢性应激效应的模型，可加速颞叶癫痫（TLE）电刺激杏仁核点燃大鼠模型中的癫痫发生。本研究考察了糖皮质激素受体的盐皮质激素（MR）和糖皮质激素（GR）亚型对该效应的相对贡献。将10 - 13周龄的雌性非癫痫Wistar大鼠在左杏仁核植入双极电极。五个治疗组接受快速杏仁核点燃：水对照（n = 9）、CS处理组（6 mg/100 ml添加到饮用水中；n = 9）、CS + 螺内酯（MR拮抗剂，50 mg/kg皮下注射；n = 9）、CS + 米非司酮（GR拮抗剂，25 mg/kg皮下注射；n = 9）以及CS + 两种拮抗剂（n = 7）。在整个点燃期，大鼠每天两次注射溶剂或相关拮抗剂。实验组在达到“完全点燃状态”（Racine，1972）所需的刺激次数上有显著差异（方差分析，F(4,38)=2.73，p = 0.04）。与水对照组相比，CS处理组的杏仁核点燃加速（完全点燃的平均刺激次数：45.2对86.5，p < 0.01）。这种加速被MR和GR拮抗剂处理所抑制（平均刺激次数：69.6和70.4，分别与CS组相比p = 0.04和0.04），这些组的点燃率与水处理组无显著差异（分别为p = 0.26和0.29）。MR和GR拮抗剂治疗组的点燃率彼此无显著差异（p = 0.93），与联合治疗组也无显著差异（平均刺激次数：62.8，分别为p = 0.59和0.54）。本研究表明，高亲和力（MR）和低亲和力（GR）糖皮质激素受体的激活均参与介导CS诱导的杏仁核点燃癫痫发生加速。
