Chang H P, Lindberg F P, Wang H L, Huang A M, Lee E H
Graduate Institute of Life Sciences, National Defense Medical Center, Taipei, Taiwan, Republic of China.
Learn Mem. 1999 Sep-Oct;6(5):448-57. doi: 10.1101/lm.6.5.448.
Previously, we have demonstrated that integrin-associated protein (IAP) mRNA level is approximately fourfold higher in rats showing good retention performance (600 sec) than rats showing poor retention performance (< 80 sec) in an inhibitory avoidance learning paradigm. In the present study, we have used the gene-targeted IAP-deficient mice to further investigate the role of IAP involved in memory formation and hippocampal long-term potentiation (LTP) in vivo. Results revealed that there was a significant impairment in memory retention and a significant reduction in the magnitude of LTP in IAP-deficient mice when compared with the wild-type and heterozygote mice, whereas the wild-type and heterozygote animals did not show marked differences on these measures. Furthermore, the impairment in retention performance of IAP-deficient mice was not due to different sensitivities of these animals to the electric shock. When we examined locomotor activity and rotarod treadmill performance, no differences were observed among these three groups of animals either. Western blot analysis confirmed the lack of IAP protein in IAP-deficient mice, whereas IAP expression was similar in both the wild-type and heterozygote controls. These results together demonstrate that IAP plays an important role in the process of memory formation and synaptic plasticity in mice.
此前,我们已经证明,在抑制性回避学习范式中,表现出良好记忆保持能力(600秒)的大鼠体内整合素相关蛋白(IAP)的mRNA水平大约是表现出较差记忆保持能力(<80秒)的大鼠的四倍。在本研究中,我们使用基因靶向的IAP缺陷小鼠进一步研究IAP在体内记忆形成和海马长时程增强(LTP)中的作用。结果显示,与野生型和杂合子小鼠相比,IAP缺陷小鼠在记忆保持方面存在显著损伤,LTP的幅度也显著降低,而野生型和杂合子动物在这些指标上没有明显差异。此外,IAP缺陷小鼠记忆保持能力的损伤并非由于这些动物对电击的敏感性不同。当我们检测运动活性和转棒跑步机表现时,这三组动物之间也未观察到差异。蛋白质印迹分析证实IAP缺陷小鼠中缺乏IAP蛋白,而野生型和杂合子对照中的IAP表达相似。这些结果共同表明,IAP在小鼠记忆形成和突触可塑性过程中发挥重要作用。