Ramos-Remus César, González-Castañeda Rocio E, González-Perez Oscar, Luquin Sonia, García-Estrada Joaquin
Department of Rheumatology, Centro Medico Nacional de Occidente del Instituto Mexicano del Seguro Social, Guadalajara, México.
J Investig Med. 2002 Nov;50(6):458-64. doi: 10.1136/jim-50-06-06.
High glucocorticoid serum levels and prednisone (PDN) therapy have been associated with depression, posttraumatic stress disorder, and some types of cognitive dysfunction in humans.
The aim of this study was to assess whether chronic (90 days) PDN administration produces disturbance in learning and memory retention associated with neuronal degeneration and cerebral glial changes.
Male Wistar rats were studied. Controls received 0.1 ml distilled water vehicle orally. The PDN group was treated orally with 5 mg/kg/d PDN, which is equivalent to moderate doses used in clinical settings. Learning and memory retention were assessed with the Morris water maze. The index of degenerated neurons as well as the number and cytoplasmic transformation of astrocytes and microglia cells were evaluated in the prefrontal cortex and the CA1 hippocampus.
PDN-treated rats showed a significant delay of 20% in learning and memory retention as compared with controls. In addition, in the PDN group, the neuronal degeneration index was two times higher in the prefrontal cortex, and approximately 10 times higher in the CA1 hippocampus, than in control animals. The number and cytoplasmic transformation of astrocytes were also significantly higher in the PDN group than in control animals. In the PDN-treated group, isolectin-B4-labeled microglia cells were higher in the prefrontal cortex but not in the hippocampus.
These results suggest that chronic exposure to PDN produces learning and memory impairment, reduces neural viability, and increases glial reactivity in cerebral regions with these cognitive functions.
高糖皮质激素血清水平和泼尼松（PDN）治疗与人类的抑郁症、创伤后应激障碍以及某些类型的认知功能障碍有关。
本研究旨在评估慢性（90天）给予PDN是否会导致与神经元变性和脑胶质细胞变化相关的学习和记忆保持障碍。
对雄性Wistar大鼠进行研究。对照组口服0.1 ml蒸馏水载体。PDN组口服5 mg/kg/d的PDN，这相当于临床使用的中等剂量。使用莫里斯水迷宫评估学习和记忆保持能力。评估前额叶皮质和海马CA1区的神经元变性指数以及星形胶质细胞和小胶质细胞的数量和细胞质变化。
与对照组相比，接受PDN治疗的大鼠在学习和记忆保持方面显著延迟了20%。此外，在PDN组中，前额叶皮质的神经元变性指数比对照动物高两倍，海马CA1区则高约10倍。PDN组中星形胶质细胞的数量和细胞质变化也显著高于对照动物。在接受PDN治疗的组中，异凝集素-B4标记的小胶质细胞在前额叶皮质中较多，但在海马中没有。
这些结果表明，长期接触PDN会导致学习和记忆障碍，降低神经活力，并增加具有这些认知功能的脑区中的胶质细胞反应性。
