Cell and Developmental Biology, School of Medicine, University of Colorado Anschutz Medical Campus, Aurora, CO, USA.
Sci Rep. 2011;1:137. doi: 10.1038/srep00137. Epub 2011 Nov 2.
Down syndrome (DS) is the most common form of congenital intellectual disability. Although DS involves multiple disturbances in various tissues, there is little doubt that in terms of quality of life cognitive impairment is the most serious facet and there is no effective treatment for this aspect of the syndrome. The Ts65Dn mouse model of DS recapitulates multiple aspects of DS including cognitive impairment. Here the Ts65Dn mouse model of DS was evaluated in an associative learning paradigm based on olfactory cues. In contrast to disomic controls, trisomic mice exhibited significant deficits in olfactory learning. Treatment of trisomic mice with the acetylcholinesterase inhibitor galantamine resulted in a significant improvement in olfactory learning. Collectively, our study indicates that olfactory learning can be a sensitive tool for evaluating deficits in associative learning in mouse models of DS and that galantamine has therapeutic potential for improving cognitive abilities.
唐氏综合征(DS)是最常见的先天性智力障碍形式。尽管 DS 涉及多种组织的多种紊乱,但毫无疑问,在生活质量方面,认知障碍是最严重的方面,而且对这种综合征没有有效的治疗方法。TS65DN 小鼠模型再现了包括认知障碍在内的多种 DS 方面。在这里,我们在基于嗅觉线索的联想学习范式中评估了 TS65DN 小鼠模型的 DS。与二倍体对照相比,三倍体小鼠在嗅觉学习中表现出明显的缺陷。用乙酰胆碱酯酶抑制剂加兰他敏治疗三倍体小鼠可显著改善嗅觉学习。总的来说,我们的研究表明,嗅觉学习可以作为评估 DS 小鼠模型联想学习缺陷的敏感工具,加兰他敏具有改善认知能力的治疗潜力。