title: MRI characterization of paranodal junction failure and related spinal cord changes in mice.
abstract: The paranodal junction is a specialized axon-glia contact zone that is important for normal neuronal activity and behavioral locomotor function in the central nervous system (CNS). Histological examination has been the only method for detecting pathological paranodal junction conditions. Recently, diffusion tensor MRI (DTI) has been used to detect microstructural changes in various CNS diseases. This study was conducted to determine whether MRI and DTI could detect structural changes in the paranodal junctions of the spinal cord in cerebroside sulfotransferase knock-out (CST-KO) mice. Here, we showed that high-resolution MRI and DTI characteristics can reflect paranodal junction failure in CST-KO mice. We found significantly lower T1 times and significantly higher T2 times in the spinal cord MRIs of CST-KO mice as compared to wild-type (WT) mice. Spinal cord DTI showed significantly lower axial diffusivity and significantly higher radial diffusivity in CST-KO mice as compared to WT mice. In contrast, the histological differences in the paranodal junctions of WT and CST-KO mice were so subtle that electron microscopy or immunohistological analyses were necessary to detect them. We also measured gait disturbance in the CST-KO mice, and determined the conduction latency by electrophysiology. These findings demonstrate the potential of using MRI and DTI to evaluate white matter disorders that involve paranodal junction failure.
authors.affiliation: Department of Orthopaedic Surgery, Keio University School of Medicine, Tokyo, Japan.
authors.forename: Morito
authors.initials: M
authors.lastname: Takano
authors.forename: Keigo
authors.initials: K
authors.lastname: Hikishima
authors.forename: Kanehiro
authors.initials: K
authors.lastname: Fujiyoshi
authors.forename: Shinsuke
authors.initials: S
authors.lastname: Shibata
authors.forename: Akimasa
authors.initials: A
authors.lastname: Yasuda
authors.forename: Tsunehiko
authors.initials: T
authors.lastname: Konomi
authors.forename: Akiko
authors.initials: A
authors.lastname: Hayashi
authors.forename: Hiroko
authors.initials: H
authors.lastname: Baba
authors.forename: Koichi
authors.initials: K
authors.lastname: Honke
authors.forename: Yoshiaki
authors.initials: Y
authors.lastname: Toyama
authors.forename: Hideyuki
authors.initials: H
authors.lastname: Okano
authors.forename: Masaya
authors.initials: M
authors.lastname: Nakamura
mesh_terms: D000818:Animals; D001369:Axons / Q000473:pathology*; D056324:Diffusion Tensor Imaging; D051379:Mice; D018345:Mice, Knockout; D009413:Nerve Fibers, Myelinated / Q000473:pathology; D009457:Neuroglia / Q000473:pathology*; D009474:Neurons / Q000473:pathology*; D013116:Spinal Cord / Q000473:pathology* / Q000503:physiopathology; D015238:Sulfotransferases / Q000235:genetics
chemical_list: D015238:Sulfotransferases; C020556:galactosylceramide sulfotransferase