Young Jared W, Kerr Lorraine E, Kelly John S, Marston Hugh M, Spratt Christopher, Finlayson Keith, Sharkey John
Astellas CNS Research in Edinburgh, The University of Edinburgh, The Chancellor's Building, 49 Little France Crescent, Edinburgh EH16 4SB, UK.
Neuropharmacology. 2007 Feb;52(2):634-45. doi: 10.1016/j.neuropharm.2006.09.006. Epub 2006 Nov 13.
Impoverished odour recognition and memory are amongst the earliest symptoms observed in mild cognitive impairment, Alzheimer's disease and schizophrenia, and have been advocated as early disease bio-markers. Although transgenic animals modelling disease pathologies continually emerge, there remains a paucity of tasks to examine olfactory working memory in mice. The present studies describe a mouse odour span task, which assesses the ability to remember increasing numbers of odours. Since caspase-3 is highly expressed throughout the olfactory system, we postulated that mice over-expressing this apoptogenic protein would exhibit impaired performance in the odour span task. Mice over-expressing human caspase-3 (Tg) exhibited age-independent deficits in olfactory working memory (6-18 months) compared with wild-type littermates, requiring longer for task acquisition and exhibiting impaired asymptotic performance, with reduced span lengths, lower accuracy and increased error rates. These impairments appeared to be selective for working memory, as Tg mice had no deficits in odour discriminatory ability or in locomotor measures. Importantly, nicotine, which improves working memory span in man, reversed the deficits exhibited by Tg mice. In conclusion, the mouse odour span task can detect subtle changes in olfactory working memory induced by genetic manipulation and drug administration and therefore should be applied to animal models of neurological disease.
嗅觉识别和记忆受损是轻度认知障碍、阿尔茨海默病和精神分裂症最早出现的症状之一，并且已被倡导作为早期疾病生物标志物。尽管不断出现模拟疾病病理的转基因动物，但用于检测小鼠嗅觉工作记忆的任务仍然很少。本研究描述了一种小鼠气味跨度任务，该任务评估记忆越来越多气味的能力。由于半胱天冬酶-3在整个嗅觉系统中高度表达，我们推测过表达这种促凋亡蛋白的小鼠在气味跨度任务中表现会受损。与野生型同窝小鼠相比，过表达人半胱天冬酶-3（Tg）的小鼠在嗅觉工作记忆方面表现出与年龄无关的缺陷（6至18个月），任务获取所需时间更长，渐近表现受损，跨度长度缩短，准确性降低且错误率增加。这些损伤似乎对工作记忆具有选择性，因为Tg小鼠在气味辨别能力或运动测量方面没有缺陷。重要的是，尼古丁可改善人类的工作记忆跨度，它逆转了Tg小鼠表现出的缺陷。总之，小鼠气味跨度任务可以检测到由基因操作和药物给药引起的嗅觉工作记忆的细微变化，因此应应用于神经疾病的动物模型。
