Myelin injury induces axonal transport impairment but not AD-like pathology in the hippocampus of cuprizone-fed mice.

Junjun Sun,Hong Zhou,Qingguo Ren,Feng Bai,Zhijun Zhang

doi:10.18632/oncotarget.8981

Junjun Sun, Hong Zhou + Show 3 more

Open Access

https://doi.org/10.18632/oncotarget.8981

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Journal: Oncotarget	Publication Date: Apr 25, 2016
Citations: 13	License type: cc-by

Affiliation: Zhongda Hospital Southeast University

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.

Highlights

Multiple sclerosis (MS) is a progressive neurological disorder of young adults, characterized by myelin destruction and neurodegeneration in the central nervous system (CNS) [1]
Our results suggest that demyelination might lead to the impairment of neuronal transport, but not cause increased level of hyperphosphorylated tau and beta amyloid
The results showed that the cuprizone-fed mice had no anxiety and depression-like behaviors, displayed as that there was no difference between the cuprizonefed mice and control mice in the open field test (Figure 1A-1C), elevated plus maze (EPM) (Figure 1D-1E), and sucrose preference test (Figure 1F)

Summary

Introduction

Multiple sclerosis (MS) is a progressive neurological disorder of young adults, characterized by myelin destruction and neurodegeneration in the central nervous system (CNS) [1]. We found the mild impairment of learning ability in cuprizone-fed mice and the decreased expression of myelin basic protein (MBP) in the 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.

Results

Conclusion