Nutritional Neuroscience and Aging, Pennington Biomedical Research Center, 6400 Perkins Rd., Baton Rouge, LA 70808, USA.
Behav Brain Res. 2011 Dec 1;225(2):415-25. doi: 10.1016/j.bbr.2011.07.051. Epub 2011 Aug 5.
One of a family of devastating lysosomal storage disorders, Krabbe disease is characterized by demyelination, psychosine accumulation, and inflammation. Affected infants rarely survive longer than 2 years. Using the twitcher mouse model of the disease, this study evaluated the potential of intrastriatal injection of adipose or bone marrow-derived mesenchymal stromal cells (MSCs) as a treatment option. Neonatal pups were injected with MSCs at 3-4 days of age and subjected to a battery of behavioral tests beginning at 15 days. While MSC injection failed to increase lifespan of twitchers, improvements in rotarod performance and twitching severity were observed at 27-38 days of age using MSCs derived from bone marrow. This study tested several different tasks developed in adult mice for evaluation of disease progression in immature twitchers. Rotarod was both reliable and extremely sensitive. Automated gait analysis using the Treadscan program was also useful for early evaluation of differences prior to overt gait dysfunction. Finally, this study represents the first use of the Stone T-maze in immature mice. Validation of rotarod and automated gait analysis for detection of subtle differences in disease progression is important for early stage efforts to develop treatments for juvenile disorders.
一种破坏性溶酶体贮积症家族，克拉伯病的特征是脱髓鞘、神经肌醇积累和炎症。受影响的婴儿很少能存活超过 2 年。本研究使用该病的抽搐鼠模型，评估了向纹状体内部注射脂肪或骨髓来源的间充质基质细胞（MSCs）作为治疗选择的可能性。新生幼鼠在 3-4 天大时接受 MSCs 注射，并从 15 天大开始进行一系列行为测试。虽然 MSC 注射未能延长抽搐鼠的寿命，但在用骨髓衍生的 MSCs 治疗时，在 27-38 天大时观察到旋转棒性能和抽搐严重程度的改善。本研究测试了几种在成年小鼠中开发的不同任务，以评估未成熟抽搐鼠的疾病进展。旋转棒既可靠又非常敏感。使用 Treadscan 程序进行的自动步态分析也可用于在明显步态功能障碍之前对差异进行早期评估。最后，本研究首次在未成熟小鼠中使用 Stone T-迷宫。旋转棒和自动步态分析对检测疾病进展中细微差异的验证，对于早期开发青少年疾病治疗方法的努力非常重要。
