Brightwell J J, Gallagher M, Colombo P J
Neuroscience Program, Tulane University, New Orleans, LA 70118, USA.
Neurobiol Learn Mem. 2004 Jan;81(1):19-26. doi: 10.1016/j.nlm.2003.08.001.
Recent evidence has shown that abnormal signal transduction is related to non-pathological memory impairment among aged subjects. Members of the CREB family of transcription factors contain enhancers (i.e., CREB1) and repressors (i.e., CREB2) of transcription and interact with numerous signaling proteins to mediate the transition from short-term to long-term memory. In this study, quantitative Western blotting was used to determine the levels of CREB1 and CREB2 in homogenates from hippocampi of individual 6- and 24-month-old male Long-Evans rats trained first on a place-learning task in the Morris water maze, then on a transfer task. Based on spatial memory performance, aged rats were characterized into two groups; aged-unimpaired rats (AU) had scores within the range of the young (Y) and aged-impaired rats (AI) fell outside of that range. Overall, CREB1 protein was significantly lower in aged rats in comparison with young rats. Aposteriori analysis showed that this difference was due to a significant decrease in CREB1 levels among aged-impaired rats, whereas aged-unimpaired rats had CREB1 levels comparable to young rats. There was no significant change in levels of CREB2 protein between young and aged rats. These results show that the dysregulation of CREB1 protein may contribute to the spatial memory deficits observed among some aged subjects.
最近有证据表明，异常信号转导与老年受试者的非病理性记忆损伤有关。转录因子CREB家族成员包含转录增强子（即CREB1）和转录抑制子（即CREB2），并与众多信号蛋白相互作用，以介导从短期记忆到长期记忆的转变。在本研究中，采用定量蛋白质免疫印迹法测定了6个月和24个月大的雄性Long-Evans大鼠海马匀浆中CREB1和CREB2的水平。这些大鼠首先在莫里斯水迷宫中进行位置学习任务训练，然后进行转移任务训练。根据空间记忆表现，将老年大鼠分为两组；老年未受损大鼠（AU）的得分在年轻大鼠（Y）的范围内，而老年受损大鼠（AI）的得分超出该范围。总体而言，与年轻大鼠相比，老年大鼠的CREB1蛋白显著降低。事后分析表明，这种差异是由于老年受损大鼠中CREB1水平显著降低，而老年未受损大鼠的CREB1水平与年轻大鼠相当。年轻大鼠和老年大鼠之间CREB2蛋白水平没有显著变化。这些结果表明，CREB1蛋白的失调可能导致一些老年受试者出现空间记忆缺陷。
