title: Axonal transport rate decreased at the onset of optic neuritis in EAE mice.
abstract: Optic neuritis is frequently the first symptom of multiple sclerosis (MS), an inflammatory demyelinating neurodegenerative disease. Impaired axonal transport has been considered as an early event of neurodegenerative diseases. However, few studies have assessed the integrity of axonal transport in MS or its animal models. We hypothesize that axonal transport impairment occurs at the onset of optic neuritis in experimental autoimmune encephalomyelitis (EAE) mice. In this study, we employed manganese-enhanced MRI (MEMRI) to assess axonal transport in optic nerves in EAE mice at the onset of optic neuritis. Axonal transport was assessed as (a) optic nerve Mn(2+) accumulation rate (in % signal change/h) by measuring the rate of increased total optic nerve signal enhancement, and (b) Mn(2+) transport rate (in mm/h) by measuring the rate of change in optic nerve length enhanced by Mn(2+). Compared to sham-treated healthy mice, Mn(2+) accumulation rate was significantly decreased by 19% and 38% for EAE mice with moderate and severe optic neuritis, respectively. The axonal transport rate of Mn(2+) was significantly decreased by 43% and 65% for EAE mice with moderate and severe optic neuritis, respectively. The degree of axonal transport deficit correlated with the extent of impaired visual function and diminished microtubule-associated tubulins, as well as the severity of inflammation, demyelination, and axonal injury at the onset of optic neuritis.
authors.affiliation: Department of Physics, Washington University, St. Louis, MO 63130, USA.
authors.forename: Tsen-Hsuan
authors.initials: TH
authors.lastname: Lin
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Joong Hee
authors.initials: JH
authors.lastname: Kim
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Carlos
authors.initials: C
authors.lastname: Perez-Torres
authors.affiliation: Department of Chemistry, Washington University, St. Louis, MO 63130, USA.
authors.forename: Chia-Wen
authors.initials: CW
authors.lastname: Chiang
authors.affiliation: Divison of Biostatistics, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Kathryn
authors.initials: K
authors.lastname: Trinkaus
authors.affiliation: Department of Neurology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA.
authors.forename: Anne H
authors.initials: AH
authors.lastname: Cross
authors.affiliation: Department of Radiology, Washington University School of Medicine, St. Louis, MO 63110, USA; Hope Center for Neurological Disorders, Washington University School of Medicine, St. Louis, MO 63110, USA. Electronic address: ssong@wustl.edu.
authors.forename: Sheng-Kwei
authors.initials: SK
authors.lastname: Song
mesh_terms: D000818:Animals; D001370:Axonal Transport / Q000502:physiology*; D004681:Encephalomyelitis, Autoimmune, Experimental / Q000378:metabolism / Q000503:physiopathology*; D007089:Image Enhancement; D008279:Magnetic Resonance Imaging / Q000379:methods*; D008345:Manganese; D051379:Mice; D008810:Mice, Inbred C57BL; D009902:Optic Neuritis / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology*; D014792:Visual Acuity / Q000502:physiology*
chemical_list: D008345:Manganese
keywords: Axonal transport; Manganese-enhanced MRI; Optic neuritis