Huentelman Matthew J, Stephan Dietrich A, Talboom Joshua, Corneveaux Jason J, Reiman David M, Gerber Jill D, Barnes Carol A, Alexander Gene E, Reiman Eric M, Bimonte-Nelson Heather A
Neurogenomics Division, The Translational Genomics Research Institute, Phoenix, Arizona 85004, USA.
Behav Neurosci. 2009 Feb;123(1):218-23. doi: 10.1037/a0014260.
Previously, utilizing a series of genome-wide association, brain imaging, and gene expression studies we implicated the KIBRA gene and the RhoA/ROCK pathway in hippocampal-mediated human memory. Here we show that peripheral administration of the ROCK inhibitor hydroxyfasudil improves spatial learning and working memory in the rodent model. This study supports the action of ROCK on learning and memory, suggests the potential value of ROCK inhibition for the promotion of cognition in humans, and highlights the powerful potential of unbiased genome-wide association studies to inform potential novel uses for existing pharmaceuticals.
此前,通过一系列全基因组关联研究、脑成像研究和基因表达研究,我们发现KIBRA基因以及RhoA/ROCK信号通路与海马体介导的人类记忆有关。在此我们表明,向啮齿动物模型外周给予ROCK抑制剂法舒地尔可改善其空间学习和工作记忆。这项研究支持了ROCK对学习和记忆的作用,提示了ROCK抑制在促进人类认知方面的潜在价值,并突出了无偏倚全基因组关联研究在为现有药物发掘潜在新用途方面的强大潜力。