Smittkamp Susan E, Spalding Heather N, Brown Jordan W, Yeh Hung-Wen, Stanford John A
Department of Molecular & Integrative Physiology, University of Kansas Medical Center, Kansas City, KS 66160, United States.
The Kansas Intellectual and Developmental Disabilities Research Center, University of Kansas Medical Center, Kansas City, KS 66160, United States.
Physiol Behav. 2014 Feb 10;125:17-20. doi: 10.1016/j.physbeh.2013.11.010. Epub 2013 Nov 27.
Most preclinical studies of amyotrophic lateral sclerosis (ALS) have focused on spinal symptoms, despite the importance of bulbar deficits in progression of the disease. We sought to determine how bulbar deficits are related to spinal deficits and survival in the SOD1-G93A rat model of ALS. We examined forelimb and hindlimb grip force and tongue motility in SOD1-G93A rats using statistical cluster analysis. Decrements in forelimb grip force, hindlimb grip force, and tongue motility were used to cluster affected rats into groups. The analysis clustered one group that exhibited primarily forelimb deficits (forelimb group) and a second group that exhibited forelimb and tongue motility deficits (forelimb+bulbar group). The analysis did not identify a distinct hindlimb phenotype group because all SOD1-G93A rats exhibited deficits in hindlimb grip force. Rats in the forelimb+bulbar group exhibited earlier and greater forelimb deficits, and earlier mortality than rats without bulbar deficits. Hindlimb deficits were similar in both groups. There was a significant correlation between forelimb grip force and tongue motility deficits, but not between forelimb and hindlimb deficits. These data extend clinical findings of a more rapid disease progression in individuals with bulbar symptoms to the SOD1-G93A rat model of ALS.
尽管延髓功能障碍在肌萎缩侧索硬化症（ALS）疾病进展中具有重要性，但大多数ALS临床前研究都集中在脊髓症状上。我们试图确定在SOD1-G93A ALS大鼠模型中，延髓功能障碍与脊髓功能障碍及存活情况之间的关系。我们使用统计聚类分析检查了SOD1-G93A大鼠的前肢和后肢握力以及舌运动能力。根据前肢握力、后肢握力和舌运动能力的下降情况，将受影响的大鼠聚类分组。分析将一组主要表现为前肢功能障碍的大鼠（前肢组）和另一组表现为前肢及舌运动能力障碍的大鼠（前肢+延髓组）区分开来。分析未识别出一个明显的后肢表型组，因为所有SOD1-G93A大鼠均表现出后肢握力下降。前肢+延髓组的大鼠比无延髓功能障碍的大鼠表现出更早且更严重的前肢功能障碍，以及更早的死亡。两组的后肢功能障碍相似。前肢握力与舌运动能力障碍之间存在显著相关性，但前肢与后肢功能障碍之间无显著相关性。这些数据将有延髓症状个体疾病进展更快的临床发现扩展至SOD1-G93A ALS大鼠模型。
