Plaschke Konstanze, Feindt Johanna, Djuric Zdenka, Heiland Sabine, Autschbach Frank, Lewicka Sabina, Martin Eike, Bardenheuer Hubert J, Nawroth Peter P, Bierhaus Angelika
Clinic of Anaesthesiology, University of Heidelberg, Im Neuenheimer Feld 110, D-69120, Heidelberg, Germany.
Stress. 2006 Jun;9(2):97-106. doi: 10.1080/10253890600691551.
We investigated whether long-lasting stress induced by chronic glucocorticoid (GC) exposure affects activation of brain NF-kappaB and whether these changes are related to functional deterioration and structural changes in the rat hippocampus. Psychometric investigations were conducted using a holeboard test system in 28 one-year-old male Wistar rats. Thereafter, rats were divided into three groups for daily administration of 10 mg corticosterone (treatment) or sesame oil (placebo = sham control for effects of the vehicle) for 60 days. Additional control rats did not receive any treatment or handling until the end of the experiment. Behavioural and cognitive changes were tested again in the holeboard system. Rat body weights and corticosterone concentrations in plasma, hippocampus and urine were determined and adrenal glands were investigated histopathologically. Hippocampal concentrations of corticosterone, NF-kappaB and I-kappaBalpha were determined using RIA, EMSA and Western blotting techniques, respectively. Structural changes in rat hippocampus were measured using magnetic resonance imaging techniques. High peripheral corticosterone concentrations after chronic treatment led to significant reductions in rat body weight. Significant atrophy of both adrenal glands with marked histological deterioration was detected. Furthermore, an increase in hippocampal corticosterone concentrations was observed after chronic administration. Chronic corticosterone treatment also significantly altered behaviour and working and reference memory capacity without changing hippocampal structure. Daily injections of sesame oil in the placebo group, however, were also sufficient to reduce the pellet-finding time. However, neither in the corticosterone group nor in the placebo group were behavioural changes paralleled by significant changes in brain NF-kappaB activation and I-kappaBalpha expression. Thus, cognitive alterations in rats seen after chronic corticosterone exposure are not paralleled by hippocampal NF-kappaB modulation.
我们研究了慢性糖皮质激素（GC）暴露所诱导的长期应激是否会影响大脑中核因子κB（NF-κB）的激活，以及这些变化是否与大鼠海马体的功能退化和结构改变有关。对28只一岁雄性Wistar大鼠使用洞板测试系统进行心理测量研究。此后，将大鼠分为三组，分别每日给予10mg皮质酮（治疗组）或芝麻油（安慰剂=溶剂效应的假对照组），持续60天。另外的对照大鼠在实验结束前不接受任何治疗或处理。在洞板系统中再次测试行为和认知变化。测定大鼠体重以及血浆、海马体和尿液中的皮质酮浓度，并对肾上腺进行组织病理学检查。分别使用放射免疫分析（RIA）、电泳迁移率变动分析（EMSA）和蛋白质免疫印迹技术测定海马体中皮质酮、NF-κB和I-κBα的浓度。使用磁共振成像技术测量大鼠海马体的结构变化。慢性治疗后外周皮质酮浓度升高导致大鼠体重显著下降。检测到双侧肾上腺明显萎缩，伴有明显的组织学恶化。此外，慢性给药后观察到海马体皮质酮浓度升高。慢性皮质酮治疗还显著改变了行为以及工作和参考记忆能力，但未改变海马体结构。然而，安慰剂组每日注射芝麻油也足以缩短找到食丸的时间。然而，无论是皮质酮组还是安慰剂组，行为变化均未伴随着大脑NF-κB激活和I-κBα表达的显著变化。因此，慢性皮质酮暴露后大鼠出现的认知改变与海马体NF-κB调节无关。
