Advancing the understanding of behaviors associated with Bacille Calmette Guérin infection using multivariate analysis.

Advancing the understanding of behaviors associated with Bacille Calmette Guérin infection using multivariate analysis.
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DOI:
10.1016/j.bbi.2014.09.018
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发表时间:
2015-02
影响因子:
15.1
通讯作者:
Kelley, Keith W.
Kelley, Keith W.
中科院分区:
医学1区
文献类型:
--
作者:
Rodriguez-Zas, Sandra L.;Nixon, Scott E.;Lawson, Marcus A.;Mccusker, Robert H.;Southey, Bruce R.;O'Connor, Jason C.;Dantzer, Robert;Kelley, Keith W.

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小鼠卡介苗(BCG)炎症模型中的行为指标已经被单独研究;然而,对不同BCG水平的行为差异以及BCG治疗组内小鼠到小鼠的差异只有部分了解。本研究的目的是:1)使用多元方法对卡介苗炎症模型中的疾病和抑郁样行为有一个全面的了解;2)探索卡介苗治疗组之间和组内小鼠之间的行为差异。实验第0天给予成年小鼠0 mg(生理盐水)、5 mg或10 mg BCG(BCG治疗组分别为BCG0、BCG5和BCG10)。疾病指标包括第0天至第2天和第2天至第5天之间的体重变化,以及第6天测量的水平运动和垂直活动(站立)。类抑郁指标包括第6天强迫游泳试验和尾部悬吊试验中的不动持续时间和第7天蔗糖偏好试验中的蔗糖消耗量。与单独分析指标相比,同时考虑互补的疾病和抑郁样指标可以更准确地描述与卡介苗治疗相关的行为变化以及小鼠到小鼠的变化。单变量和多变量分析证实了卡介苗治疗组在试验早期体重变化方面的差异。卡介苗治疗组之间在抑郁样行为方面的显著差异在第5天后仍可测量到。对于疾病和抑郁样指标,证明了多变量模型解释行为指标之间的相关性并提高相对于单变量模型的分析精度的潜力。无监督的学习方法揭示了所考虑的疾病和类似抑郁的指标提供的补充信息。使用交叉验证的监督学习方法证实了卡介苗治疗组和组内小鼠之间的细微差异,这些差异是通过考虑疾病和类似抑郁的指标来确定的。这些发现支持对疾病和类似抑郁的指标进行多变量和多维分析的建议,以增强对与感染相关的行为变化的系统了解。
Behavioral indicators in the murine Bacille Calmette Guérin (BCG) model of inflammation have been studied individually; however, the variability of the behaviors across BCG levels and the mouse-to-mouse variation within BCG-treatment group are only partially understood. The objectives of this study were: 1) to gain a comprehensive understanding of sickness and depression-like behaviors in a BCG model of inflammation using multivariate approaches, and 2) to explore behavioral differences between BCG-treatment groups and among mice within group. Adult mice were challenged with either 0mg (saline), 5mg or 10mg of BCG (BCG-treatment groups: BCG0, BCG5, or BCG10, respectively) at Day 0 of the experiment. Sickness indicators included body weight changes between Day 0 and Day 2 and between Day 2 and Day 5, and horizontal locomotor activity and vertical activity (rearing) measured at Day 6. Depression-like indicators included duration of immobility in the forced swim test and in the tail suspension test at Day 6 and sucrose consumption in the sucrose preference test at Day 7. The simultaneous consideration of complementary sickness and depression-like indicators enabled a more precise characterization of behavioral changes associated with BCG-treatment and of mouse-to-mouse variation, relative to the analysis of indicators individually. Univariate and multivariate analyses confirmed differences between BCG-treatment groups in weight change early on the trial. Significant differences between BCG-treatment groups in depression-like behaviors were still measurable after Day 5. The potential for multivariate models to account for the correlation between behavioral indicators and to augment the analytical precision relative to univariate models was demonstrated both for sickness and for depression-like indicators. Unsupervised learning approaches revealed the complementary information provided by the sickness and depression-like indicators considered. Supervised learning approaches using cross-validation confirmed subtle differences between BCG-treatment groups and among mice within group identified by the consideration of sickness and depression-like indicators. These findings support the recommendation for multivariate and multidimensional analyses of sickness and depression-like indicators to augment the systemic understanding of the behavioral changes associated with infection.
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