title: Impairment of learning and memory in TAG-1 deficient mice associated with shorter CNS internodes and disrupted juxtaparanodes.
abstract: 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-1 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.
authors.affiliation: Department of Basic Science, University of Crete Medical School, and Institute of Molecular Biology and Biotechnology, Heraklion, Greece.
authors.forename: Maria
authors.initials: M
authors.lastname: Savvaki
authors.forename: Theofanis
authors.initials: T
authors.lastname: Panagiotaropoulos
authors.forename: Antonis
authors.initials: A
authors.lastname: Stamatakis
authors.forename: Irene
authors.initials: I
authors.lastname: Sargiannidou
authors.forename: Pinelopi
authors.initials: P
authors.lastname: Karatzioula
authors.forename: Kazutada
authors.initials: K
authors.lastname: Watanabe
authors.forename: Fotini
authors.initials: F
authors.lastname: Stylianopoulou
authors.forename: Domna
authors.initials: D
authors.lastname: Karagogeos
authors.forename: Kleopas A
authors.initials: KA
authors.lastname: Kleopa