Pawlowski Traci L, Bellush Linda L, Wright Amy W, Walker Jon P, Colvin Robert A, Huentelman Matthew J
The Translational Genomics Research Institute, Neurogenomics Division, 445 N Fifth Street, Phoenix, AZ 85004, USA.
Brain Res. 2009 Feb 23;1256:101-10. doi: 10.1016/j.brainres.2008.12.039. Epub 2008 Dec 25.
As humans age, cognitive performance decreases differentially across individuals. This age-related decline in otherwise healthy individuals is likely due to the interaction of multiple factors including genetics and environment. We hypothesized that altered spatial memory performance in genetically similar mice could be in part due to differential gene expression patterns in the hippocampus. To investigate this we utilized Morris water maze (MWM) testing in a group of young (3 months) and aged (24 months) C57BL/J male mice. Two sub-groups were identified in the aged animals; one in which MWM performance was not significantly different when compared to the young animals (aged-unimpaired; "AU") and one in which performance was significantly different by 1.5 standard deviations from the mean (aged-impaired; "AI"). One week after testing was completed the entire hippocampus was collected from six each of AU, AI and young mice and their gene expression profiles were compared using Affymetrix microarrays. Benjamini and Hochberg FDR correction at p<0.05 identified 18 genes differentially expressed between the AI and AU mice. The correlation between behavioral deficits and gene expression patterning allows a better understanding of how altered gene expression in the hippocampus contributes to accelerated age-related cognitive decline and delineates between gene expression changes associated with normal aging vs. memory performance.
随着人类年龄的增长，个体间的认知能力会出现不同程度的下降。在其他方面健康的个体中，这种与年龄相关的衰退可能是多种因素相互作用的结果，包括基因和环境。我们推测，基因相似的小鼠空间记忆能力的改变可能部分归因于海马体中不同的基因表达模式。为了对此进行研究，我们对一组年轻（3个月）和年老（24个月）的C57BL/J雄性小鼠进行了莫里斯水迷宫（MWM）测试。在年老的动物中识别出两个亚组；一组与年轻动物相比，MWM测试表现无显著差异（年老未受损组；“AU”），另一组表现与平均值相差1.5个标准差，差异显著（年老受损组；“AI”）。测试完成一周后，从每组六只的AU、AI和年轻小鼠中收集整个海马体，并用Affymetrix微阵列比较它们的基因表达谱。采用Benjamini和Hochberg错误发现率校正，p<0.05时，确定AI和AU小鼠之间有18个基因差异表达。行为缺陷与基因表达模式之间的相关性有助于更好地理解海马体中基因表达的改变如何导致与年龄相关的认知衰退加速，并区分与正常衰老相关的基因表达变化和与记忆表现相关的基因表达变化。
