Key Laboratory of Animal Models and Human Disease Mechanisms of Yunnan Province, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650201, China.
National Research Facility for Phenotypic & Genetic Analysis of Model Animals (Primate Facility), Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, Yunnan 650107, China.
Cereb Cortex. 2023 Sep 26;33(19):10303-10321. doi: 10.1093/cercor/bhad283.
Impairments in spatial navigation in humans can be preclinical signs of Alzheimer's disease. Therefore, cognitive tests that monitor deficits in spatial memory play a crucial role in evaluating animal models with early stage Alzheimer's disease. While Chinese tree shrews (Tupaia belangeri) possess many features suitable for Alzheimer's disease modeling, behavioral tests for assessing spatial cognition in this species are lacking. Here, we established reward-based paradigms using the radial-arm maze and cheeseboard maze for tree shrews, and tested spatial memory in a group of 12 adult males in both tasks, along with a control water maze test, before and after bilateral lesions to the hippocampus, the brain region essential for spatial navigation. Tree shrews memorized target positions during training, and task performance improved gradually until reaching a plateau in all 3 mazes. However, spatial learning was compromised post-lesion in the 2 newly developed tasks, whereas memory retrieval was impaired in the water maze task. These results indicate that the cheeseboard task effectively detects impairments in spatial memory and holds potential for monitoring progressive cognitive decline in aged or genetically modified tree shrews that develop Alzheimer's disease-like symptoms. This study may facilitate the utilization of tree shrew models in Alzheimer's disease research.
人类空间导航能力的损伤可能是阿尔茨海默病的临床前迹象。因此,监测空间记忆缺陷的认知测试在评估早期阿尔茨海默病动物模型方面发挥着至关重要的作用。虽然中国树鼩(Tupaia belangeri)具有许多适合阿尔茨海默病建模的特征,但这种物种的空间认知行为测试却缺乏。在这里,我们使用放射臂迷宫和奶酪棋盘迷宫为树鼩建立了基于奖励的范式,并在双侧海马损伤前后,对 12 只成年雄性树鼩进行了这两种任务以及对照水迷宫测试,以测试空间记忆。树鼩在训练过程中记住目标位置,并且在所有 3 个迷宫中,任务表现逐渐提高,直到达到稳定水平。然而,在新开发的 2 个任务中,空间学习在损伤后受损,而在水迷宫任务中,记忆检索受损。这些结果表明,奶酪棋盘任务有效地检测到空间记忆的损伤,并且有可能监测到出现类似阿尔茨海默病症状的老年或基因修饰树鼩的认知能力进行性下降。这项研究可能有助于利用树鼩模型进行阿尔茨海默病研究。