Longitudinal measures of cognition in the Ts65Dn mouse: Refining windows and defining modalities for therapeutic intervention in Down syndrome.
Longitudinal measures of cognition in the Ts65Dn mouse: Refining windows and defining modalities for therapeutic intervention in Down syndrome.
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Ts65Dn 小鼠认知的纵向测量：细化窗口并定义唐氏综合症治疗干预的方式。
DOI：
10.1016/j.expneurol.2016.02.005
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发表时间：
2016
影响因子：
5.3
通讯作者：
Haydar,TarikF
中科院分区：
文献类型：
--
作者：
Olmos-Serrano,JLuis;Tyler,WilliamA;Cabral,HowardJ;Haydar,TarikF
小鼠模型提供了唐氏综合症成人学习和记忆变化的洞察力，但从未深入评估这些异常是如何随着时间的推移而发展的。为了解决这一缺陷，我们在Ts65Dn小鼠模型中进行了一项从出生到成年后期的纵向行为研究，通过一系列广泛的测试来衡量个体学习和记忆缺陷的出现和连续性。我们的结果首次表明，获得新生儿和围产期里程碑的速度与成年后的认知表现相关。此外，我们发现，终生行为指数将小鼠分成不同的基因。我们的扩展评估显示，认知灵活性降低，通过逆转学习来衡量，是Ts65Dn幼鼠和老年小鼠最健壮的学习和记忆损伤。此外，我们发现，反转学习随着年龄的增长而退化，因此是研究与年龄相关的认知能力下降的有用生物标记物。总之，我们的结果表明，旨在恢复Ts65Dn认知功能的临床前研究应该同时针对新生儿里程碑和成年后的反向学习。在这里，我们提供了这类方法的量化框架。
Mouse models have provided insights into adult changes in learning and memory in Down syndrome, but an in-depth assessment of how these abnormalities develop over time has never been conducted. To address this shortcoming, we conducted a longitudinal behavioral study from birth until late adulthood in the Ts65Dn mouse model to measure the emergence and continuity of learning and memory deficits in individuals with a broad array of tests. Our results demonstrate for the first time that the pace at which neonatal and perinatal milestones are acquired is correlated with later cognitive performance as an adult. In addition, we find that life-long behavioral indexing stratifies mice within each genotype. Our expanded assessment reveals that diminished cognitive flexibility, as measured by reversal learning, is the most robust learning and memory impairment in both young and old Ts65Dn mice. Moreover, we find that reversal learning degrades with age and is therefore a useful biomarker for studying age-related decline in cognitive ability. Altogether, our results indicate that preclinical studies aiming to restore cognitive function in Ts65Dn should target both neonatal milestones and reversal learning in adulthood. Here we provide the quantitative framework for this type of approach.