Parachikova A, Cotman C W
Institute for Brain Aging and Dementia, University of California, 1113 Gillespie Neuroscience Research Facility, Irvine, CA 92697-4540, USA.
Neurobiol Dis. 2007 Nov;28(2):143-53. doi: 10.1016/j.nbd.2007.07.001. Epub 2007 Jul 10.
Alzheimer disease (AD) is characterized by the presence of plaques and tangles in parallel with progressive cognitive decline. The underlying cause of the cognitive decline is unknown. The purpose of this study was to identify factors that could affect learning and memory using the Tg2576 mouse model of AD. Un-biased GeneChip analysis at the time-point coinciding with the onset of behavioral deficits but prior to plaque deposition revealed that Tg2576 show altered gene expression for a number of molecules including the chemokine CXCL12. We show that this chemokine's mRNA, protein and receptor are downregulated in this mouse model coinciding with cognitive deficits. Furthermore, we demonstrate that CXCL12 levels are decreased in AD patients as compared to controls. To determine if CXCL12 might be related to impaired learning and memory, we chronically treated young non-transgenic mice with an antagonist to the CXCL12 receptor to simulate the reduction seen in transgenic animals. Treated animals showed selectively impaired learning and memory suggesting a potential role for this chemokine in cognitive functioning.
阿尔茨海默病（AD）的特征是出现斑块和缠结，同时伴有进行性认知衰退。认知衰退的根本原因尚不清楚。本研究的目的是利用AD的Tg2576小鼠模型确定可能影响学习和记忆的因素。在行为缺陷开始但斑块沉积之前的时间点进行的无偏基因芯片分析显示，Tg2576小鼠中包括趋化因子CXCL12在内的许多分子的基因表达发生了改变。我们发现，在该小鼠模型中，这种趋化因子的mRNA、蛋白质和受体与认知缺陷同时下调。此外，我们证明与对照组相比，AD患者体内CXCL12水平降低。为了确定CXCL12是否可能与学习和记忆受损有关，我们用CXCL12受体拮抗剂对年轻的非转基因小鼠进行长期治疗，以模拟转基因动物中观察到的CXCL12水平降低。接受治疗的动物表现出选择性学习和记忆受损，表明这种趋化因子在认知功能中可能发挥作用。
