Spangler E L, Waggie K S, Hengemihle J, Roberts D, Hess B, Ingram D K
Molecular Physiology and Genetics Section, Nathan W. Shock Laboratories, National Institutes on Aging, National Institutes of Health, Baltimore, MD 21224.
Neurobiol Aging. 1994 May-Jun;15(3):319-28. doi: 10.1016/0197-4580(94)90027-2.
Male Fischer-344 (F344) and Brown Norway (BN) rats 7-, 13-, and 24-month-old and their F344 x BN hybrid (F1) 7-, 13-, 24- and 31-month-old were tested in a behavioral battery (15-min and 24-h locomotor activity, inclined screen, rod suspension, rotorod, shock-motivated learning in a straight runway and 14-unit T maze). Necropsy was performed 3 days later and the results rated for pathology (i.e., severity of lesions observed). Age-related performance declines were observed in all behavioral tests except 15-min locomotor activity. Strain effects were observed in 15-min (BN more active than F344 and F1) and 24-h locomotor activity test (F344 more active than BN and F1 strains); rotorod performance (F344 fell more than BN and F1); and in all measures [errors (E), runtime (RT)], shock frequency (SF), and duration (SD)] in the 14-unit T maze (F344 worse than BN, BN worse than F1). T maze performance of 31-month-old F1 rats was deficient in RT, SD, and SF but E performance was equivalent to that of 7-month-old F1 rats. In a second experiment, only 7- and 31-month-old F1 rats were tested in the 14-unit T maze and the results obtained in Experiment 1 were replicated. Gross necropsy revealed age and strain effects in the number of lesions observed and the mean ratings of pathology. The 24-month-old F344 rats exhibited the greatest number of lesions and had the highest ratings (generally observed as chronic nephrosis and enlarged spleens characteristic of mononuclear cell leukemia). BN rats exhibited a high incidence of hydronephrosis at all age levels. While experiencing less obvious pathology, F1 rats experienced a significant number of lesions in the 31-month-old group. Pathology ratings correlated with behavioral performance but only for a few tests (e.g., SD and RT in 14 unit T maze in 24-month-old F344). Thus, behavioral performance declined with age and the battery of tests differentiated between the strains tested (in general, F344 worse than BN; BN worse than F1). The correlation of pathology ratings at gross necropsy with behavior did not appear to be systematic, suggesting that morbidity was not responsible for the age-related performance declines. However, more extensive evaluation of the relationship of age-related changes in health status to behavior with larger samples of rats is suggested.
对7月龄、13月龄和24月龄的雄性费希尔344（F344）大鼠和棕色挪威（BN）大鼠，以及7月龄、13月龄、24月龄和31月龄的F344×BN杂交（F1）大鼠进行了一系列行为测试（15分钟和24小时运动活动、倾斜屏幕、棒悬挂、转棒试验、直线跑道电击驱动学习以及14单元T迷宫试验）。3天后进行尸检，并对病理结果进行评分（即观察到的病变严重程度）。除15分钟运动活动外，在所有行为测试中均观察到与年龄相关的行为表现下降。在15分钟（BN比F344和F1更活跃）和24小时运动活动测试（F344比BN和F1品系更活跃）、转棒试验表现（F344比BN和F1掉落更多）以及14单元T迷宫的所有测量指标[错误次数（E）、运行时间（RT）]、电击频率（SF）和持续时间（SD）中观察到品系效应（F344比BN差，BN比F1差）。31月龄F1大鼠在T迷宫中的RT、SD和SF表现较差，但E表现与7月龄F1大鼠相当。在第二个实验中，仅对7月龄和31月龄的F1大鼠进行了14单元T迷宫测试，并重复了实验1的结果。大体尸检显示，在观察到的病变数量和病理平均评分方面存在年龄和品系效应。24月龄F344大鼠的病变数量最多，评分最高（通常表现为慢性肾病和单核细胞白血病特征性的脾脏肿大）。BN大鼠在所有年龄组中肾盂积水的发生率都很高。虽然F1大鼠的病理表现不太明显，但在31月龄组中也出现了大量病变。病理评分与行为表现相关，但仅在少数测试中如此（例如，24月龄F344大鼠在14单元T迷宫中的SD和RT）。因此，行为表现随年龄下降，并且该系列测试区分了所测试的品系（一般来说，F344比BN差；BN比F1差）。大体尸检时病理评分与行为之间的相关性似乎不具有系统性，这表明发病率并非与年龄相关的行为表现下降的原因。然而，建议使用更大样本的大鼠对健康状况的年龄相关变化与行为之间的关系进行更广泛的评估。
