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Introduction: Mammalian animals with reduced GH and IGF-1 signaling have extended lifespans compared to control siblings, and maintain a normal cognitive functions to advanced age.Lewis dwarf rats have a spontaneous mutation that causes a selective, 90% reduction in pituitary production of GH and a decline in plasma GH to barely detectable levels, resulting in a reduction in plasma IGF-Ⅰ.The purpose of this study was to investigate the differences in cognition and memory ability between Lewis dwarf and normal rats with aging,and to explore the possible molecular mechanisms.Methods: Middle-aged (10-12 months) and old (18-20months) Lewis dwarf and normal rats (male) were subjected to the Morris water maze aimed at differentiating their cognitive and memory behaviors.Plasma levels of GH and IGF-1 were detected with RIA and Elisa.Local expression of GH/IGF-1, CREB1 and microRNAs in the hippocampi of the animals were examined by Western blot, miRNA microarray and quantitative RT-PCR, respectively.Result: The plasma levels of GH and IGF-1in Lewis dwarf rats were less than one half of those in normal rats, but no differences could be found between middle-aged and old animals in each groups.Hidden platform version of water maze showed that there were no significant differences in latency of spatial learning between Lewis dwarf and normal rats in either middle-aged or old.Although in probe trial the dwarf rats showed a trend to swim slower, the difference was not statistically significant.Western analysis, MicroRNA microarray and quantitative RT-PCR illustrated that the levels of hippocampal GH/IGF-1, CREB1, miR-27b, miR-26b, miR-181d and miR-138-1* in Lewis dwarf were as high as in normal rats, and these miRNAs were negative correlation with CREB1 expression.Bioinformatic analysis showed that, CREB 1 mRNA contains complementary sequences to the miR-27b, miR-26b, miR-18 1d and miR-138-1* seed regions in rat.Conclusion: Although Lewis dwarf rats lose their circulation GH and IGF-Ⅰ, the local GH/IGF-Ⅰ regulation as well as levels of CREB1 and miRNAs in hippocampus are not significantly affected, indicating that maintenance of cognitive and memory functions in rats is related to local rather than system GH/IGF-Ⅰ regulation,and miRNAs (miR-27b, miR-26b, miR-181d and miR-138-1 *) are involved in regulation of cognitive and memory functions in Lewis rats.