Age-related cognitive impairments in mice with a conditional ablation of the neural cell adhesion molecule
Age-related cognitive impairments in mice with a conditional ablation of the neural cell adhesion molecule
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DOI：
10.1101/lm.030064.112
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发表时间：
2013-04-01
影响因子：
2
通讯作者：
Sandi, Carmen
中科院分区：
文献类型：
--
作者：
Bisaz, Reto;Boadas-Vaello, Pere;Sandi, Carmen
大多数神经可塑性机制支持认知，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粘附分子（NCAM）在结构和功能可塑性中起着关键作用，并且是调节认知和情感行为所必需的。然而，衰老是否与NCAM改变有关，而NCAM改变可能导致与年龄相关的认知能力下降，目前尚不清楚。在这项研究中，我们确定了条件性NCAM缺陷小鼠是否对年龄相关的认知和情绪变化表现出更大的脆弱性。我们评估了海马和内侧前额叶皮质（mPFC）的NCAM表达水平，并在Morris水迷宫的延迟匹配到位测试和T迷宫的延迟强化交替测试中表征了成年和老年条件性NCAM缺陷小鼠及其年龄匹配的野生型同窝仔的表现。尽管野生型小鼠的衰老与海马和mPFC中NCAM表达水平的同种型特异性降低相关，但这些小鼠在工作/情节样记忆表现中仅表现出轻度损伤。然而，老年条件性NCAM缺陷小鼠在延迟匹配到位和延迟强化交替测试中均显示出明显的损伤。重要的是，老年NCAM缺陷小鼠在这些工作/情节样记忆任务中的缺陷不能归因于焦虑样行为的增加或自发活动的差异。综上所述，这些数据表明，减少NCAM表达的前脑可能是一个关键因素，发生认知功能障碍在老化过程中。
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.