Behavioral Neuroscience and Comparative Psychology Division, Department of Psychology, Arizona Alzheimer's Consortium, Arizona State University, 950 S. McAllister Ave., PO Box 871104, Tempe, AZ, 85287, USA.
Arizona Alzheimer's Consortium, 4745 N 7th St, Phoenix, AZ, 85014, USA.
Sci Rep. 2022 Aug 26;12(1):14596. doi: 10.1038/s41598-022-18415-1.
The TgF344 rat model of Alzheimer's disease (AD) provides a comprehensive neuropathology presentation, with age-dependent development of tau tangles, amyloid-beta (A[Formula: see text]) plaques, neuronal loss, and increased gliosis. The behavioral trajectory of this model, particularly relating to spatial learning and memory, has yet to be fully characterized. The current experiment evaluated spatial working and reference memory performance, as well as several physiological markers of health, at 3 key age points in female TgF344-AD rats: 6-months, 9-months, and 12-months. At 6 months of age, indications of working and reference memory impairments were observed in transgenic (Tg) rats on the water radial-arm maze, a complex task that requires working and reference memory simultaneously; at 12 months old, Tg impairments were observed for two working memory measures on this task. Notably, no impairments were observed at the 9-month timepoint on this maze. For the Morris maze, a measure of spatial reference memory, Tg rats demonstrated significant impairment relative to wildtype (WT) controls at all 3 age-points. Frontal cortex, entorhinal cortex, and dorsal hippocampus were evaluated for A[Formula: see text] expression via western blot in Tg rats only. Analyses of A[Formula: see text] expression revealed age-dependent increases in all 3 regions critical to spatial learning and memory. Measures of physiological health, including heart, uterine, and body weights, revealed unique age-specific outcomes for female Tg rats, with the 9-month timepoint identified as critical for further research within the trajectory of AD-like behavior, physiology, and pathology.
TgF344 阿尔茨海默病（AD）大鼠模型提供了全面的神经病理学表现，具有与年龄相关的tau 缠结、淀粉样β（A[Formula: see text]）斑块、神经元丢失和神经胶质增生的发展。该模型的行为轨迹，特别是与空间学习和记忆有关的轨迹，尚未得到充分描述。目前的实验评估了雌性 TgF344-AD 大鼠在 3 个关键年龄点的空间工作和参考记忆表现，以及几种健康生理标志物：6 个月、9 个月和 12 个月。在 6 个月大时，转基因（Tg）大鼠在水放射臂迷宫上表现出工作和参考记忆障碍的迹象，这是一项需要同时进行工作和参考记忆的复杂任务；在 12 个月大时，Tg 大鼠在该任务的两个工作记忆测量上表现出损伤。值得注意的是，在该迷宫上 9 个月大时没有观察到损伤。对于空间参考记忆的 Morris 迷宫，Tg 大鼠在所有 3 个年龄点都表现出相对于野生型（WT）对照的显著损伤。仅在 Tg 大鼠中通过 Western blot 评估前额叶皮层、内嗅皮层和背侧海马中的 A[Formula: see text]表达。A[Formula: see text]表达分析显示，所有 3 个对空间学习和记忆至关重要的区域均随年龄增长而增加。包括心脏、子宫和体重在内的生理健康测量结果显示，Tg 大鼠具有独特的年龄特异性结果，9 个月大的时间点被确定为 AD 样行为、生理学和病理学轨迹内进一步研究的关键。
