Peking University Institute of Mental Health (Sixth Hospital), Beijing, China.
National Clinical Research Center for Mental Disorders & NHC Key Laboratory of Mental Health (Peking University), Beijing, China.
J Neurosci Res. 2024 Jan;102(1):e25265. doi: 10.1002/jnr.25265.
The olfactory working memory capacity (OWMC) paradigm is able to detect cognitive deficits in 5XFAD mice (an animal model of Alzheimer's disease [TG]) as early as 3 months of age, while other behavioral paradigms detect cognitive deficits only at 4-5 months of age. Therefore, we aimed to demonstrate that the OWMC paradigm is more sensitive and consistent in the early detection of declines in cognitive function than other commonly used behavioral paradigms. The prefrontal cortex (PFC), retrosplenial cortex (RSC), subiculum (SUB), and amygdala (AMY) of 5XFAD mice were harvested and subjected to immunostaining to detect the expression of β-amyloid (Aβ). Additionally, we compared the performance of 3-month-old male 5XFAD mice on common behavioral paradigms for assessing cognitive function (i.e., the open field [OF] test, novel object recognition [NOR] test, novel object location [NOL] test, Y-maze, and Morris water maze [MWM]) with that on the OWMC task. In the testing phase of the OWMC task, we varied the delay periods to evaluate the working memory capacity (WMC) of wild-type (WT) mice. Significant amyloid plaque deposition was observed in the PFC, RSC, SUB, and AMY of 3-month-old male 5XFAD mice. However, aside from the OWMC task, the other behavioral tests failed to detect cognitive deficits in 5XFAD mice. Additionally, to demonstrate the efficacy of the OWMC task in assessing WMC, we varied the retention delay periods; we found that the WMC of WT mice decreased with longer delay periods. The OWMC task is a sensitive and robust behavioral assay for detecting changes in cognitive function.
嗅觉工作记忆容量 (OWMC) 范式能够早在 3 个月大时就检测到 5XFAD 小鼠（阿尔茨海默病 [TG] 的动物模型）的认知缺陷，而其他行为范式仅在 4-5 个月大时才能检测到认知缺陷。因此，我们旨在证明 OWMC 范式在早期检测认知功能下降方面比其他常用行为范式更敏感和一致。我们收获了 5XFAD 小鼠的前额叶皮层 (PFC)、后扣带回皮层 (RSC)、下托 (SUB) 和杏仁核 (AMY)，并进行免疫染色以检测 β-淀粉样蛋白 (Aβ) 的表达。此外，我们比较了 3 月龄雄性 5XFAD 小鼠在常见的认知功能评估行为范式（即开阔场 [OF] 测试、新物体识别 [NOR] 测试、新物体位置 [NOL] 测试、Y 迷宫和 Morris 水迷宫 [MWM]）上的表现与 OWMC 任务。在 OWMC 任务的测试阶段，我们改变了延迟时间来评估野生型 (WT) 小鼠的工作记忆容量 (WMC)。我们观察到 3 月龄雄性 5XFAD 小鼠的 PFC、RSC、SUB 和 AMY 中有明显的淀粉样斑块沉积。然而，除了 OWMC 任务外，其他行为测试未能检测到 5XFAD 小鼠的认知缺陷。此外，为了证明 OWMC 任务在评估 WMC 方面的功效，我们改变了保留延迟时间；我们发现 WT 小鼠的 WMC 随着延迟时间的延长而降低。OWMC 任务是一种灵敏且强大的行为测定方法，用于检测认知功能的变化。
