Department of Neuro-/Pathology, Translational Neurodegeneration Research and Neuropathology Lab, University of Oslo (UiO) and Oslo University Hospital (OUS), Oslo, Norway.
Current address: University of Lübeck, Lübeck, Germany.
J Alzheimers Dis. 2020;75(4):1301-1317. doi: 10.3233/JAD-200161.
Spatial memory dysfunction has been demonstrated in mouse models of Alzheimer's disease (AD) which is consistent with the clinical finding that the early signature of AD includes difficulties in the formation and/or storage of a memory. A stored memory-a long term memory-can be modulated via process called as memory retrieval that can either lead toward memory reconsolidation or even memory extinction.
We aim to shed light on the fate of the spatial memory during memory reactivation and memory extinction using a water maze task.
In Set-up I, we trained 3-month-old mice (wild-type mice and mice with cerebral β-amyloidosis) and assessed the fate of remote memory after four months of retention interval (RI). In Set-up II, we performed an early-extensive training at 2 months of age, retrained the same mice at 3 months of age, introduced four months of RI, and finally assessed remote spatial memory at 7 months of age.
We find in β-amyloidosis mice that memory reactivation problems were detectable at 7 months of age and were alleviated by cognitive overtraining. Similarly, forgetting of remote spatial memory was also minimized by cognitive overtraining. Finally, we show that the cognitive training facilitates the recovery of the reactivated spatial memory while reducing the ability to form new spatial memory in AD mice.
This result may explain the rationality behind the cognitive reserve observed in AD patients and elderly with severe β-amyloidosis not corresponding to the actual low dementia symptoms.
阿尔茨海默病（AD）的小鼠模型已经表现出空间记忆功能障碍，这与 AD 的临床发现一致，即 AD 的早期特征包括记忆形成和/或存储困难。存储的记忆——长期记忆——可以通过记忆检索过程进行调节，这既可以导致记忆再巩固，也可以导致记忆消除。
我们旨在通过水迷宫任务阐明在记忆再激活和记忆消除期间空间记忆的命运。
在设置 I 中，我们训练了 3 个月大的小鼠（野生型小鼠和大脑β-淀粉样蛋白病变小鼠），并在 4 个月的保留间隔（RI）后评估了远程记忆的命运。在设置 II 中，我们在 2 个月大时进行了早期广泛训练，在 3 个月大时重新训练相同的小鼠，引入了 4 个月的 RI，最后在 7 个月大时评估了远程空间记忆。
我们在β-淀粉样蛋白病变小鼠中发现，7 个月大时可检测到记忆再激活问题，认知过度训练可缓解这些问题。同样，认知过度训练也可最大限度地减少远程空间记忆的遗忘。最后，我们表明认知训练促进了再激活空间记忆的恢复，同时降低了 AD 小鼠形成新空间记忆的能力。
这一结果可能解释了 AD 患者和严重β-淀粉样蛋白病变的老年人中观察到的认知储备的合理性，而与实际的低痴呆症状并不相符。
