期刊
MOLECULAR AND CELLULAR NEUROSCIENCE
卷 39, 期 3, 页码 478-490出版社
ACADEMIC PRESS INC ELSEVIER SCIENCE
DOI: 10.1016/j.mcn.2008.07.025
关键词
Spatial learning and memory; Novel object recognition; Spontaneous motor activity; Footprint analysis; Nociception; Voltage gated potassium channels; Juxtaparanodes; Nodes of Ranvier; Caspr2
资金
- Cyprus Research Promotion Foundation
- ELA Foundation
- Foundation for Research and Technology
- Ministry of Education of Greece
- National Multiple Sclerosis Society of USA [RG3457A2/1]
- Special Account for Research Grants of the University of Athens
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.
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