Laboratory of Behavioral Genetics, Brain Mind Institute, Ecole Polytechnique Federale de Lausanne (EPFL), 1015 Lausanne, Switzerland.
Learn Mem. 2013 Mar 15;20(4):183-93. doi: 10.1101/lm.030064.112.
Most of the mechanisms involved in neural plasticity support cognition, and aging has a considerable effect on some of these processes. The neural cell adhesion molecule (NCAM) of the immunoglobulin superfamily plays a pivotal role in structural and functional plasticity and is required to modulate cognitive and emotional behaviors. However, whether aging is associated with NCAM alterations that might contribute to age-related cognitive decline is not currently known. In this study, we determined whether conditional NCAM-deficient mice display increased vulnerability to age-related cognitive and emotional alterations. We assessed the NCAM expression levels in the hippocampus and medial prefrontal cortex (mPFC) and characterized the performance of adult and aged conditional NCAM-deficient mice and their age-matched wild-type littermates in a delayed matching-to-place test in the Morris water maze and a delayed reinforced alternation test in the T-maze. Although aging in wild-type mice is associated with an isoform-specific reduction of NCAM expression levels in the hippocampus and mPFC, these mice exhibited only mild impairments in working/episodic-like memory performance. However, aged conditional NCAM-deficient mice displayed pronounced impairments in both the delayed matching-to-place and the delayed reinforced alternation tests. Importantly, the deficits of aged NCAM-deficient mice in these working/episodic-like memory tasks could not be attributed to increased anxiety-like behaviors or to differences in locomotor activity. Taken together, these data indicate that reduced NCAM expression in the forebrain might be a critical factor for the occurrence of cognitive impairments during aging.
大多数涉及神经可塑性的机制都支持认知，而衰老对其中一些过程有相当大的影响。免疫球蛋白超家族的神经细胞黏附分子（NCAM）在结构和功能可塑性中发挥关键作用，并且需要调节认知和情绪行为。然而，衰老是否与可能导致与年龄相关的认知能力下降的 NCAM 改变有关，目前尚不清楚。在这项研究中，我们确定了条件性 NCAM 缺失小鼠是否表现出对与年龄相关的认知和情绪改变的易感性增加。我们测定了海马体和内侧前额叶皮质（mPFC）中的 NCAM 表达水平，并在 Morris 水迷宫中的延迟匹配位置测试和 T 迷宫中的延迟强化交替测试中，描述了成年和老年条件性 NCAM 缺失小鼠及其同龄野生型同窝小鼠的表现。尽管野生型小鼠的衰老与海马体和 mPFC 中 NCAM 表达水平的同工型特异性降低有关，但这些小鼠仅在工作/情景样记忆表现上出现轻度损伤。然而，老年条件性 NCAM 缺失小鼠在延迟匹配位置和延迟强化交替测试中均表现出明显的损伤。重要的是，这些工作/情景样记忆任务中老年 NCAM 缺失小鼠的缺陷不能归因于焦虑样行为的增加或运动活性的差异。总之，这些数据表明，前脑 NCAM 表达的降低可能是衰老期间认知障碍发生的关键因素。
