Luedtke Kelsey, Bouchard Sioui Maldonado, Woller Sarah A, Funk Mary Katherine, Aceves Miriam, Hook Michelle A
Department of Neuroscience and Experimental Therapeutics, Texas A&M Health Science Center , Bryan, Texas.
J Neurotrauma. 2014 Jun 15;31(12):1107-21. doi: 10.1089/neu.2013.3204. Epub 2014 May 8.
Despite an increased incidence of depression in patients after spinal cord injury (SCI), there is no animal model of depression after SCI. To address this, we used a battery of established tests to assess depression after a rodent contusion injury. Subjects were acclimated to the tasks, and baseline scores were collected before SCI. Testing was conducted on days 9-10 (acute) and 19-20 (chronic) postinjury. To categorize depression, subjects' scores on each behavioral measure were averaged across the acute and chronic stages of injury and subjected to a principal component analysis. This analysis revealed a two-component structure, which explained 72.2% of between-subjects variance. The data were then analyzed with a hierarchical cluster analysis, identifying two clusters that differed significantly on the sucrose preference, open field, social exploration, and burrowing tasks. One cluster (9 of 26 subjects) displayed characteristics of depression. Using these data, a discriminant function analysis was conducted to derive an equation that could classify subjects as "depressed" on days 9-10. The discriminant function was used in a second experiment examining whether the depression-like symptoms could be reversed with the antidepressant, fluoxetine. Fluoxetine significantly decreased immobility in the forced swim test (FST) in depressed subjects identified with the equation. Subjects that were depressed and treated with saline displayed significantly increased immobility on the FST, relative to not depressed, saline-treated controls. These initial experiments validate our tests of depression, generating a powerful model system for further understanding the relationships between molecular changes induced by SCI and the development of depression.
尽管脊髓损伤（SCI）患者中抑郁症的发病率有所增加，但目前尚无SCI后抑郁症的动物模型。为了解决这一问题，我们使用了一系列既定测试来评估啮齿动物挫伤损伤后的抑郁症。实验对象先适应各项任务，并在脊髓损伤前收集基线分数。在损伤后的第9 - 10天（急性期）和第19 - 20天（慢性期）进行测试。为了对抑郁症进行分类，将实验对象在每个行为指标上的分数在损伤的急性和慢性阶段进行平均，并进行主成分分析。该分析揭示了一个由两个成分组成的结构，解释了72.2%的个体间差异。然后用层次聚类分析对数据进行分析，识别出在蔗糖偏好、旷场试验、社交探索和挖掘任务上有显著差异的两个聚类。其中一个聚类（26个实验对象中的9个）表现出抑郁症的特征。利用这些数据，进行判别函数分析以得出一个能在第9 - 10天将实验对象分类为“抑郁”的方程。该判别函数用于第二个实验，以检验抑郁样症状是否能用抗抑郁药氟西汀逆转。氟西汀显著降低了用该方程识别出的抑郁实验对象在强迫游泳试验（FST）中的不动时间。相对于未抑郁、用生理盐水处理的对照组，抑郁且用生理盐水处理的实验对象在FST中的不动时间显著增加。这些初步实验验证了我们对抑郁症的测试，为进一步理解SCI诱导的分子变化与抑郁症发展之间的关系建立了一个强大的模型系统。
