Tsai Kuen J, Chen Shau K, Ma Yun L, Hsu Wei L, Lee Eminy H Y
Graduate Institute of Life Sciences, National Defense Medical Center, and Institute of Biomedical Sciences, Academia Sinica, Taipei 115, Taiwan, Republic of China.
Proc Natl Acad Sci U S A. 2002 Mar 19;99(6):3990-5. doi: 10.1073/pnas.062405399. Epub 2002 Mar 12.
By using differential display PCR, we have identified 98 cDNA fragments from the rat dorsal hippocampus that are expressed differentially between the fast learners and slow learners in the water maze learning task. One of these cDNA fragments encodes the rat serum- and glucocorticoid-inducible kinase (sgk) gene. Northern blot analysis revealed that the sgk mRNA level was approximately 4-fold higher in the hippocampus of fast learners than slow learners. In situ hybridization results indicated that sgk mRNA level was increased markedly in CA1, CA3, and dentate gyrus of hippocampus in fast learners. Transient transfection of the sgk mutant DNA to the CA1 area impaired, whereas transfection of the sgk wild-type DNA facilitated water maze performance in rats. These results provide direct evidence that enhanced sgk expression facilitates memory consolidation of spatial learning in rats. These results also elucidate the molecular mechanism of glucocorticoid-induced memory facilitation in mammals.
通过使用差异显示PCR技术,我们从大鼠背侧海马体中鉴定出98个cDNA片段,这些片段在水迷宫学习任务中快速学习者和慢速学习者之间存在差异表达。其中一个cDNA片段编码大鼠血清和糖皮质激素诱导激酶(sgk)基因。Northern印迹分析显示,快速学习者海马体中的sgk mRNA水平比慢速学习者高约4倍。原位杂交结果表明,快速学习者海马体的CA1、CA3和齿状回中sgk mRNA水平显著增加。将sgk突变体DNA瞬时转染到CA1区会损害大鼠的水迷宫表现,而转染sgk野生型DNA则有助于大鼠的水迷宫表现。这些结果提供了直接证据,表明sgk表达增强有助于大鼠空间学习的记忆巩固。这些结果还阐明了糖皮质激素诱导哺乳动物记忆促进的分子机制。