title: Myelin injury induces axonal transport impairment but not AD-like pathology in the hippocampus of cuprizone-fed mice.
abstract: Both multiple sclerosis (MS) and Alzheimer's disease (AD) are progressive neurological disorders with myelin injury and memory impairment. However, whether myelin impairment could cause AD-like neurological pathology remains unclear. To explore neurological pathology following myelin injury, we assessed cognitive function, the expression of myelin proteins, axonal transport-associated proteins, axonal structural proteins, synapse-associated proteins, tau and beta amyloid and the status of neurons, using the cuprizone mouse model of demyelination. We found the mild impairment of learning ability in cuprizone-fed mice and the decreased expression of myelin basic protein (MBP) in the hippocampus. And anti-LINGO-1 improved learning ability and partly restored MBP level. Furthermore, we also found kinesin light chain (KLC), neurofilament light chain (NFL) and neurofilament heavy chain (NF200) were declined in demyelinated hippocampus, which could be partly improved by treatment with anti-LINGO-1. However, we did not observe the increased expression of beta amyloid, hyperphosphorylation of tau and loss of neurons in demyelinated hippocampus. Our results suggest that demyelination might lead to the impairment of neuronal transport, but not cause increased level of hyperphosphorylated tau and beta amyloid. Our research demonstrates remyelination might be an effective pathway to recover the function of neuronal axons and cognition in MS.
authors.affiliation: Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Junjun
authors.initials: J
authors.lastname: Sun
authors.affiliation: Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Hong
authors.initials: H
authors.lastname: Zhou
authors.affiliation: Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Feng
authors.initials: F
authors.lastname: Bai
authors.affiliation: Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Qingguo
authors.initials: Q
authors.lastname: Ren
authors.affiliation: Department of Neuropsychiatry, Affiliated ZhongDa Hospital, School of Medicine, Southeast University, Nanjing, China.
authors.forename: Zhijun
authors.initials: Z
authors.lastname: Zhang
mesh_terms: D000544:Alzheimer Disease / Q000503:physiopathology; D016229:Amyloid beta-Peptides / Q000378:metabolism; D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D001370:Axonal Transport; D001369:Axons / Q000473:pathology*; D003071:Cognition / Q000187:drug effects; D003471:Cuprizone / Q000633:toxicity; D003711:Demyelinating Diseases / Q000139:chemically induced / Q000503:physiopathology*; D004195:Disease Models, Animal; D005455:Fluorescent Antibody Technique; D006624:Hippocampus / Q000473:pathology*; D006801:Humans; D016547:Kinesins; D008297:Male; D018782:Maze Learning / Q000187:drug effects; D008565:Membrane Proteins / Q000037:antagonists & inhibitors*; D051379:Mice; D008810:Mice, Inbred C57BL; D008869:Microtubule-Associated Proteins / Q000378:metabolism; D004676:Myelin Basic Protein / Q000378:metabolism; D009186:Myelin Sheath / Q000473:pathology*; D009419:Nerve Tissue Proteins / Q000037:antagonists & inhibitors*; D016900:Neurofilament Proteins / Q000378:metabolism; D010766:Phosphorylation; D016875:tau Proteins / Q000378:metabolism
chemical_list: D016229:Amyloid beta-Peptides; D000911:Antibodies, Monoclonal; C523678:LINGO1 protein, mouse; C558298:Mapt protein, mouse; C499047:Mbp protein, mouse; D008565:Membrane Proteins; D008869:Microtubule-Associated Proteins; D004676:Myelin Basic Protein; D009419:Nerve Tissue Proteins; D016900:Neurofilament Proteins; D016875:tau Proteins; C051774:neurofilament protein H; D003471:Cuprizone; D016547:Kinesins
keywords: Gerotarget; axonal transport; beta amyloid; demyelination; remyelination; tau