Liu Weilin, Li Jianhong, Li Le, Zhang Yuhao, Yang Minguang, Liang Shengxiang, Li Long, Dai Yaling, Chen Lewen, Jia Weiwei, He Xiaojun, Lin Huawei, Tao Jing
National-Local Joint Engineering Research Center of Rehabilitation Medicine Technology, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
TCM Rehabilitation Research Center of SATCM, Fujian University of Traditional Chinese Medicine, Fuzhou, China.
Front Cell Neurosci. 2022 Mar 21;16:848967. doi: 10.3389/fncel.2022.848967. eCollection 2022.
Memory generalization allows individuals to extend previously learned movement patterns to similar environments, contributing to cognitive flexibility. In Alzheimer's disease (AD), the disturbance of generalization is responsible for the deficits of episodic memory, causing patients with AD to forget or misplace things, even lose track of the way home. Cognitive training can effectively improve the cognition of patients with AD through changing thinking mode and memory flexibility. In this study, a T-shaped maze was utilized to simulate cognitive training in APP/PS1 mice to elucidate the potential mechanisms of beneficial effects after cognitive training. We found that cognitive training conducted by a T-shaped maze for 4 weeks can improve the memory generalization ability of APP/PS1 mice. The results of functional magnetic resonance imaging (fMRI) showed that the functional activity of the medial prefrontal cortex (mPFC) and hippocampus was enhanced after cognitive training, and the results of magnetic resonance spectroscopy (MRS) showed that the neurochemical metabolism of N-acetyl aspartate (NAA) and glutamic acid (Glu) in mPFC, hippocampus and reuniens (Re) thalamic nucleus were escalated. Furthermore, the functional activity of mPFC and hippocampus was negatively correlated with the escape latency in memory generalization test. Therefore, these results suggested that cognitive training might improve memory generalization through enhancing the functional activity of mPFC and hippocampus and increasing the metabolism of NAA and Glu in the brain regions of mPFC, hippocampus and Re nucleus.
记忆泛化使个体能够将先前学到的运动模式扩展到相似环境中，有助于认知灵活性。在阿尔茨海默病（AD）中，泛化障碍导致情景记忆缺陷，使AD患者忘记或错放物品，甚至迷失回家的路。认知训练可以通过改变思维模式和记忆灵活性有效改善AD患者的认知。在本研究中，利用T形迷宫对APP/PS1小鼠进行认知训练模拟，以阐明认知训练后有益效果的潜在机制。我们发现，通过T形迷宫进行4周的认知训练可以提高APP/PS1小鼠的记忆泛化能力。功能磁共振成像（fMRI）结果显示，认知训练后内侧前额叶皮质（mPFC）和海马体的功能活性增强，磁共振波谱（MRS）结果显示，mPFC、海马体和丘脑 reuniens（Re）核中N-乙酰天门冬氨酸（NAA）和谷氨酸（Glu）的神经化学代谢升高。此外，mPFC和海马体的功能活性与记忆泛化测试中的逃避潜伏期呈负相关。因此，这些结果表明，认知训练可能通过增强mPFC和海马体的功能活性以及增加mPFC、海马体和Re核脑区中NAA和Glu的代谢来改善记忆泛化。
