Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity.
Transgenic mice overexpressing the extracellular domain of NCAM are impaired in working memory and cortical plasticity.
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DOI：
10.1016/j.nbd.2011.04.008
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发表时间：
2011-08
影响因子：
6.1
通讯作者：
Maness, Patricia F.
中科院分区：
文献类型：
--
作者：
Brennaman, Leann H.;Kochlamazashvili, Gaga;Stoenica, Luminita;Nonneman, Randall J.;Moy, Sheryl S.;Schachner, Melitta;Dityatev, Alexander;Maness, Patricia F.
神经细胞粘附分子（NCAM）是神经发育的关键调节因子，在轴突和树突生长以及突触可塑性中起关键作用。NCAM表达或蛋白水解裂解的改变与人类神经精神障碍如精神分裂症、双相情感障碍和阿尔茨海默病有关，并可能导致认知功能障碍。我们已经产生过表达NCAM细胞外（EC）蛋白水解裂解片段的小鼠，据报道，该片段在精神分裂症患者的大脑中比正常大脑中增加。这些小鼠表现出受损的GABA能神经支配和前额皮质（PFC）锥体神经元上的顶端树突棘数量减少。在这里，这些NCAM-EC转基因小鼠进行行为任务和电生理测量，以确定在PFC的突触和认知功能的结构异常的影响。NCAM-EC小鼠在延迟的非匹配样本任务中表现出受损的工作记忆，这需要PFC功能，但在焦虑，嗅觉能力或社交能力方面没有表现出差异。转基因小鼠表现出受损的长时程和短时程增强的PFC，但正常的突触可塑性在海马，这表明在NCAM-EC小鼠的异常突触神经支配损害PFC的可塑性和改变工作记忆。这些发现可能对神经精神疾病中观察到的认知功能障碍有影响。
The neural cell adhesion molecule, NCAM, is a pivotal regulator of neural development, with key roles in axonal and dendritic growth and synaptic plasticity. Alterations in NCAM expression or proteolytic cleavage have been linked to human neuropsychiatric disorders such as schizophrenia, bipolar disorder and Alzheimer’s disease, and may contribute to cognitive dysfunction. We have generated mice overexpressing the NCAM extracellular (EC) proteolytic cleavage fragment which has been reported to be increased in schizophrenic versus normal brains. These mice show impaired GABAergic innervation and reduced number of apical dendritic spines on pyramidal neurons in the prefrontal cortex (PFC). Here, these NCAM-EC transgenic mice were subjected to behavioral tasks and electrophysiological measurements to determine the impact of structural abnormalities in the PFC on synaptic and cognitive functions. NCAM-EC mice exhibited impaired working memory in a delayed non-match-to-sample task, which requires PFC function, but showed no differences in anxiety, olfactory abilities, or sociability. Transgenic mice displayed impaired long- and short-term potentiation in the PFC but normal synaptic plasticity in the hippocampus, suggesting that the abnormal synaptic innervation in NCAM-EC mice impairs PFC plasticity and alters working memory. These findings may have implications for cognitive dysfunctions observed in neuropsychiatric disorders.
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DOI：
10.1080/13803390802360526
发表时间：
2009-02
影响因子：
2.2
作者：
Anderson SW;Wisnowski JL;Barrash J;Damasio H;Tranel D
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影响因子：
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作者：
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DOI：
10.1073/pnas.0308280101
发表时间：
2004-03-02
影响因子：
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作者：
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