El-Kordi Ahmed, Radyushkin Konstantin, Ehrenreich Hannelore
Division of Clinical Neuroscience, Max Planck Institute of Experimental Medicine, Göttingen, Germany.
BMC Biol. 2009 Jul 8;7:37. doi: 10.1186/1741-7007-7-37.
Executive functions, learning and attention are imperative facets of cognitive performance, affected in many neuropsychiatric disorders. Recently, we have shown that recombinant human erythropoietin improves cognitive functions in patients with chronic schizophrenia, and that it leads in healthy mice to enhanced hippocampal long-term potentiation, an electrophysiological correlate of learning and memory. To create an experimental basis for further mechanistic insight into erythropoietin-modulated cognitive processes, we employed the Five Choice Serial Reaction Time Task. This procedure allows the study of the effects of erythropoietin on discrete processes of learning and attention in a sequential fashion.
Male mice were treated for 3 weeks with erythropoietin (5,000 IU/kg) versus placebo intraperitoneally every other day, beginning at postnatal day 28. After termination of treatment, mice were started on the Five Choice Serial Reaction Time Task, with daily training and testing extending to about 3 months.Overall, a significantly higher proportion of erythropoietin-treated mice finished the task, that is, reached the criteria of adequately reacting to a 1.0 sec flash light out of five arbitrarily appearing choices. During acquisition of this capability, that is, over almost all sequential training phases, learning readouts (magazine training, operant and discriminant learning, stability of performance) were superior in erythropoietin-treated versus control mice.
Early erythropoietin treatment leads to lasting improvement of cognitive performance in healthy mice. This finding should be exploited in novel treatment strategies for brain diseases.
执行功能、学习和注意力是认知表现的重要方面，在许多神经精神疾病中都会受到影响。最近，我们发现重组人促红细胞生成素可改善慢性精神分裂症患者的认知功能，并使健康小鼠的海马体长期增强效应增强，而海马体长期增强效应是学习和记忆的一种电生理关联。为了为进一步深入了解促红细胞生成素调节的认知过程建立实验基础，我们采用了五选择连续反应时任务。该程序可以依次研究促红细胞生成素对学习和注意力离散过程的影响。
从出生后第28天开始，雄性小鼠每隔一天接受一次促红细胞生成素（5000国际单位/千克）或安慰剂腹腔注射，持续3周。治疗结束后，小鼠开始进行五选择连续反应时任务，每天训练和测试，持续约3个月。总体而言，接受促红细胞生成素治疗的小鼠完成任务的比例显著更高，即在五个任意出现的选择中，能够对1.0秒的闪光做出充分反应。在获得这种能力的过程中，即在几乎所有连续训练阶段，与对照小鼠相比，接受促红细胞生成素治疗的小鼠的学习读数（弹匣训练、操作性和辨别性学习、表现稳定性）更优。
早期促红细胞生成素治疗可使健康小鼠的认知表现得到持久改善。这一发现应在脑部疾病的新治疗策略中加以利用。
