Levy A, Dachir S, Arbel I, Kadar T
Department of Pharmacology, Israel Institute for Biological Research, Ness-Ziona.
Ann N Y Acad Sci. 1994 Jun 30;717:79-88. doi: 10.1111/j.1749-6632.1994.tb12075.x.
Stress was implied as involved in "enhanced aging," and prolonged administration of corticosterone was claimed to lead to central neuronal lesions. This study describes an animal model that simulates the steroid elevation associated with stress by a continuous slow-release administration of corticosterone, in young (3 months old) and middle-aged (12 months old) Fischer 344 rats. Plasma concentrations of corticosterone were stable throughout the day, with no diurnal variation, within the range associated with mild stress. Corticosterone prolonged treatment resulted in morphological changes mainly in the CA1, CA4, and dentate gyrus areas of the hippocampus. Middle-aged rats showed higher vulnerability to the long-term COR treatment than young ones, even when COR treatment was prolonged in young rats from 63 to 90 days. Middle-aged rats were screened before the corticosterone treatment, using the Morris water maze, and divided between cognitively "impaired" and "nonimpaired" subpopulations. Severe cognitive damage during acquisition of the eight-arm radial maze was shown, after the continuous hormonal treatment, in rats initially defined as "nonimpaired" in the Morris water maze. This animal model might be useful for testing the protective effects of drugs against brain changes and cognitive damage, during either pathological or normal aging.
应激被认为与“加速衰老”有关，且有人声称长期给予皮质酮会导致中枢神经元损伤。本研究描述了一种动物模型，该模型通过在年轻（3个月大）和中年（12个月大）的Fischer 344大鼠中持续缓慢释放皮质酮来模拟与应激相关的类固醇升高。皮质酮的血浆浓度在一整天内保持稳定，无昼夜变化，处于与轻度应激相关的范围内。皮质酮长期治疗主要导致海马体的CA1、CA4和齿状回区域出现形态学变化。中年大鼠比年轻大鼠对长期皮质酮治疗表现出更高的易感性，即使年轻大鼠的皮质酮治疗时间从63天延长到90天也是如此。在皮质酮治疗前，使用莫里斯水迷宫对中年大鼠进行筛选，并将其分为认知“受损”和“未受损”亚群。在连续激素治疗后，最初在莫里斯水迷宫中被定义为“未受损”的大鼠在八臂放射状迷宫获取过程中出现了严重的认知损伤。这种动物模型可能有助于测试药物在病理或正常衰老过程中对大脑变化和认知损伤的保护作用。
