Raber Jacob, Olsen Reid H J, Su Weiping, Foster Scott, Xing Rubing, Acevedo Summer F, Sherman Larry S
Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; Departments of Neurology and Radiation Medicine, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA; Division of Neuroscience, Oregon National Primate Research Center, 505 NW 185th Avenue, Beaverton, OR 97006, USA.
Department of Behavioral Neuroscience, Oregon Health & Science University, 3181 SW Sam Jackson Park Road, Portland, OR 97239, USA.
Behav Brain Res. 2014 Dec 15;275:146-9. doi: 10.1016/j.bbr.2014.09.010. Epub 2014 Sep 16.
CD44 is a transmembrane receptor for the glycosaminoglycan hyaluronan, a component of the extracellular matrix. CD44 is expressed by neural stem/progenitor cells, astrocytes, and some neurons but its function in the central nervous system is unknown. To determine the role of CD44 in brain function, we behaviorally analyzed CD44-null (KO) and wild-type (WT) mice. KO mice showed increased activity levels in the light-dark test and a trend toward increased activity in the open field. In addition, KO mice showed impaired hippocampus-dependent spatial memory retention in the probe trial following the first hidden-platform training day in the Morris water maze: WT mice showed spatial memory retention and spent more time in the target quadrant than any other quadrant, while KO mice did not. Although there were no genotype differences in swim speeds during the water maze training sessions with the visible or hidden platform, sensorimotor impairments were seen in other behavioral tests. In the inclined screen and balance beam tests, KO mice moved less than WT mice. In the wire hang test, KO mice also fell off of the wire faster than WT mice. In contrast, there was no genotype difference when emotional learning and memory were assessed in the passive avoidance test. These data support an important role for CD44 in locomotor and sensorimotor functions, and in spatial memory retention.
CD44是细胞外基质成分糖胺聚糖透明质酸的跨膜受体。神经干细胞/祖细胞、星形胶质细胞和一些神经元可表达CD44，但其在中枢神经系统中的功能尚不清楚。为了确定CD44在脑功能中的作用，我们对CD44基因敲除（KO）小鼠和野生型（WT）小鼠进行了行为分析。在明暗试验中，KO小鼠的活动水平增加，在旷场试验中有活动增加的趋势。此外，在莫里斯水迷宫首次隐藏平台训练日后的探索试验中，KO小鼠表现出海马依赖性空间记忆保持受损：WT小鼠表现出空间记忆保持，且在目标象限停留的时间比其他任何象限都长，而KO小鼠则不然。虽然在可见或隐藏平台的水迷宫训练期间，游泳速度没有基因型差异，但在其他行为测试中观察到感觉运动障碍。在倾斜屏幕试验和平衡木试验中，KO小鼠的移动比WT小鼠少。在悬线试验中，KO小鼠也比WT小鼠更快地从线上掉落。相比之下，在被动回避试验中评估情绪学习和记忆时，没有基因型差异。这些数据支持CD44在运动和感觉运动功能以及空间记忆保持中起重要作用。
