Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes
Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes
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DOI：
10.1016/j.mcn.2008.07.025
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发表时间：
2008-10-29
影响因子：
3.5
通讯作者：
Kleopa, Kleopas A.
中科院分区：
文献类型：
--
作者：
Savvaki, Maria;Panagiotaropoulos, Theofanis;Kleopa, Kleopas A.
细胞黏附分子Tag-1由神经元和神经胶质细胞表达，在轴突生长、迁移和发育过程中发挥作用。TAG-I对于Kv1.1/1.2钾通道和Caspr2在有髓纤维旁的聚集也是必需的。对Tag-1基因缺陷小鼠(Tag-1(-/-))的行为学检查显示，在Morris水迷宫和新物体识别测试中，认知障碍，自发运动活动减少，步态协调异常，对伤害性刺激的反应潜伏期延长。分子水平的研究发现，Caspr2和Kv1.1/1.2在海马区、内嗅皮层、小脑和嗅球的并列结节旁聚集受损，并扩散到节间。小脑和嗅球中Caspr2和Kv1.1的表达降低。此外，TAG-1(-/-)小鼠的大脑和小脑白质节间较短。检测到的分子变化可能解释了这些动物的行为缺陷和过度兴奋。(C)2008 Elsevier Inc.保留所有权利。
The cell adhesion molecule TAG-1 is expressed by neurons and glial cells and plays a role in axon outgrowth, Migration and fasciculation during development. TAG-I is also required for the clustering of Kv1.1/1.2 potassium channels and Caspr2 at the juxtaparanodes of myelinated fibers. Behavioral examination of TAG-1 deficient mice (Tag-1(-/-)) showed cognitive impairments in the Morris water maze and novel object recognition tests, reduced spontaneous motor activity, abnormal gait coordination and increased response latency to noxious stimulation. Investigation at the molecular level revealed impaired juxtaparanodal clustering of Caspr2 and Kv1.1/1.2 in the hippocampus, entorhinal cortex, cerebellum and olfactory bulb, with diffusion into the internode. Caspr2 and Kv1.1 levels were reduced in the cerebellum and olfactory bulb. Moreover, Tag-1(-/-) mice had shorter internodes in the cerebral and cerebellar white matter. The detected molecular alterations may account for the behavioural deficits and hyperexcitability in these animals. (C) 2008 Elsevier Inc. All rights reserved.