Effects of aging on behavioral assessment performance: implications for clinically relevant models of neurological disease.
Effects of aging on behavioral assessment performance: implications for clinically relevant models of neurological disease.
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DOI：
10.3171/2012.5.jns112224
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发表时间：
2012-09
影响因子：
4.1
通讯作者：
Ryan C. Turner;M. Seminerio;Zachary J Naser;J. Neal Ford;Samantha J. Martin;Rae R. Matsumoto;Charles L. Rosen;J. Huber
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文献类型：
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作者：
Ryan C. Turner;M. Seminerio;Zachary J Naser;J. Neal Ford;Samantha J. Martin;Rae R. Matsumoto;Charles L. Rosen;J. Huber
目的尽管衰老在神经系统和神经退行性疾病的发展中起作用，但在临床前研究的实验设计中，年龄的影响往往被忽视。功能评估增加了神经系统疾病动物模型的临床相关性，并增加了传统组织学方法之外的价值。然而，年龄和功能损害之间的关系还没有通过一系列的功能测试进行系统的评估。方法采用不同的感觉运动测试和行为学测试，评价衰老对幼龄动物功能表现的影响。感觉运动测量包括运动活动；旋转杆、斜面和握力测试；以及改良的神经严重程度评分。用Morris水迷宫检测学习记忆的差异，用高架加迷宫和强迫游泳试验评估焦虑样行为和抑郁样行为。结果与青年大鼠(3~4月龄)相比，老年SD大鼠(18~20月龄)在斜面试验中表现较差，在高架迷宫和强迫游泳试验中表现出明显的改变。具体地说，老年大鼠在高架迷宫中张开双臂的探索减少，在强迫游泳测试中不动时间增加。与年轻成年大鼠相比，老年大鼠的空间获得和参考记忆能力减弱。结论本研究显示幼年动物和老年动物之间存在明显的差异，这可能对临床前神经系统疾病模型的功能评估有一定的指导意义。
OBJECT Despite the role of aging in development of neurological and neurodegenerative diseases, the effects of age are often disregarded in experimental design of preclinical studies. Functional assessment increases the clinical relevance of animal models of neurological disease and adds value beyond traditional histological measures. However, the relationship between age and functional impairment has not been systematically assessed through a battery of functional tests. METHODS In this study, various sensorimotor and behavioral tests were used to evaluate effects of aging on functional performance in naive animals. Sensorimotor measures included locomotor activity; Rotarod, inclined plane, and grip-strength testing; and modified Neurological Severity Score. The Morris water maze was used to examine differences in learning and memory, and the elevated plus maze and forced swim test were used to assess anxiety-like and depressive-like behaviors, respectively. RESULTS Older Sprague-Dawley rats (18-20 months) were found to perform significantly worse on the inclined plane tests, and they exhibited alterations in elevated-plus maze and forced swim test compared with young adult rats (3-4 months). Specifically, older rats exhibited reduced exploration of open arms in elevated plus maze and higher immobility time in forced swim test. Spatial acquisition and reference memory were diminished in older rats compared with those in young adult rats. CONCLUSIONS This study demonstrates clear differences between naive young adult and older animals, which may have implications in functional assessment for preclinical models of neurological disease.