Lam Virginie, Takechi Ryusuke, Albrecht Matthew A, D'Alonzo Zachary John, Graneri Liam, Hackett Mark J, Coulson Stephanie, Fimognari Nicholas, Nesbit Michael, Mamo John C L
Curtin Health Innovation Research Institute, Faculty of Health Sciences, Curtin University, Perth, WA, Australia.
School of Public Health, Faculty of Health Sciences, Curtin University, Perth, WA, Australia.
Front Behav Neurosci. 2018 Aug 28;12:174. doi: 10.3389/fnbeh.2018.00174. eCollection 2018.
Morris water maze (MWM) is widely used to assess cognitive deficits in pre-clinical rodent models. Latency time to reach escape platform is frequently reported, but may be confounded by deficits in visual acuity, or differences in locomotor activity. This study compared performance of Senescence Accelerated Mouse Prone-Strain 8 (SAMP8) and control Senescence Accelerated Mouse Resistant-Strain 1 (SAMR1) mice in classical MWM, relative to performance in a newly developed olfactory-visual maze testing protocol. Performance indicated as the escape time to rescue platform for classical MWM testing showed that SAMP8 mice as young as 6 weeks of age did poorly relative to age-matched SAMR1 mice. The olfactory-visual maze challenge described better discriminated SAMP8 vs. SAMR1 mice than classical MWM testing, based on latency time measures. Consideration of the distance traveled rather than latency time in the classical MWM found no treatment effects between SAMP8 and SAMR1 at 40 weeks of age and the olfactory-visual measures of performance confirmed the classical MWM findings. Longitudinal (repeat) assessment of SAMP8 and SAMR1 performance at 6, 20, 30, and 40 weeks of age in the olfactory-visual testing protocol showed no age-associated deficits in SAMP8 mice to the last age end-point indicated. Collectively, the results from this study suggest the olfactory-visual testing protocol may be advantageous compared to classical MWM as it avoids potential confounders of visual impairment in some strains of mice and indeed, may offer insight into cognitive and behavioral deficits that develop with advanced age in the widely used SAMP8 murine model.
莫里斯水迷宫（MWM）被广泛用于评估临床前啮齿动物模型中的认知缺陷。到达逃生平台的潜伏期时间经常被报告，但可能会因视力缺陷或运动活动差异而混淆。本研究比较了衰老加速小鼠易患8型（SAMP8）和对照衰老加速小鼠抗性1型（SAMR1）小鼠在经典MWM中的表现，相对于在新开发的嗅觉-视觉迷宫测试方案中的表现。在经典MWM测试中，以到达救援平台的逃生时间表示的表现表明，年仅6周龄的SAMP8小鼠相对于年龄匹配的SAMR1小鼠表现较差。基于潜伏期时间测量，嗅觉-视觉迷宫挑战比经典MWM测试能更好地区分SAMP8和SAMR1小鼠。在经典MWM中考虑行进距离而非潜伏期时间，发现在40周龄时SAMP8和SAMR1之间没有治疗效果，并且嗅觉-视觉表现测量结果证实了经典MWM的发现。在嗅觉-视觉测试方案中对6、20、30和40周龄的SAMP8和SAMR1表现进行纵向（重复）评估，结果表明到最后指定的年龄终点，SAMP8小鼠没有与年龄相关的缺陷。总体而言，本研究结果表明，与经典MWM相比，嗅觉-视觉测试方案可能具有优势，因为它避免了某些品系小鼠视觉损伤的潜在混杂因素，并且确实可能有助于深入了解在广泛使用的SAMP8小鼠模型中随着年龄增长而出现的认知和行为缺陷。
