MANF Is Neuroprotective in Early Stages of EAE, and Elevated in Spinal White Matter by Treatment With Dexamethasone

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dc.contributor.author Nam, Jinhan
dc.contributor.author Koppinen, Tapani K.
dc.contributor.author Voutilainen, Merja H.
dc.date.accessioned 2021-08-19T12:16:01Z
dc.date.available 2021-08-19T12:16:01Z
dc.date.issued 2021-07-07
dc.identifier.citation Nam , J , Koppinen , T K & Voutilainen , M H 2021 , ' MANF Is Neuroprotective in Early Stages of EAE, and Elevated in Spinal White Matter by Treatment With Dexamethasone ' , Frontiers in Cellular Neuroscience , vol. 15 , 640084 . https://doi.org/10.3389/fncel.2021.640084
dc.identifier.other PURE: 167717685
dc.identifier.other PURE UUID: 782949b7-39a7-438a-a512-5542767c3fec
dc.identifier.other WOS: 000674883600001
dc.identifier.other ORCID: /0000-0002-8658-7687/work/98709548
dc.identifier.uri http://hdl.handle.net/10138/333311
dc.description.abstract Multiple sclerosis (MS) is a progressive autoimmune disease characterized by T-cell mediated demyelination in central nervous system (CNS). Experimental autoimmune encephalomyelitis (EAE) is a widely used in vivo disease model of MS. Glucocorticoids such as dexamethasone (dex) function as immunosuppressants and are commonly used to treat acute exacerbations of MS. Dex is also often used as a positive control in EAE studies, as it has been shown to promote motor behavior, inhibit immune cell infiltration into the CNS and regulate the activation of glial cell in EAE. This study further validated the effects of intravenously administrated dex by time-dependent fashion in EAE. Dex postponed clinical signs and motor defects in early stages of EAE. Histological analysis revealed that the degeneration of myelin and axons, as well as the infiltration of peripheral immune cells into the white matter of spinal cord was inhibited by dex in early stages of EAE. Additionally, dex-treatment delayed the neuroinflammatory activation of microglia and astrocytes. Furthermore, this study analyzed the expression of the neurotrophic factor mesencephalic astrocyte-derived neurotrophic factor (MANF) in EAE, and the effect of treatment with dex on MANF-expression. We show that in dex-treated EAE mice expression MANF increased within myelinated areas of spinal cord white matter. We also show that intravenous administration with hMANF in EAE mice improved clinical signs and motor behavior in the early stage of EAE. Our report gives insight to the progression of EAE by providing a time-dependent analysis. Moreover, this study investigates the link between MANF and the EAE model, and shows that MANF is a potential drug candidate for MS. en
dc.format.extent 13
dc.language.iso eng
dc.relation.ispartof Frontiers in Cellular Neuroscience
dc.rights cc_by
dc.rights.uri info:eu-repo/semantics/openAccess
dc.subject MS
dc.subject EAE
dc.subject MANF
dc.subject dexamethasone
dc.subject neuroinflammation
dc.subject UPR
dc.subject Reactive glia
dc.subject EXPERIMENTAL AUTOIMMUNE ENCEPHALOMYELITIS
dc.subject ENDOPLASMIC-RETICULUM STRESS
dc.subject MULTIPLE-SCLEROSIS
dc.subject NEUROTROPHIC FACTOR
dc.subject EXPERIMENTAL-MODELS
dc.subject ER STRESS
dc.subject LESIONS
dc.subject GLUCOCORTICOIDS
dc.subject PREVENTION
dc.subject MODULATOR
dc.subject 3112 Neurosciences
dc.title MANF Is Neuroprotective in Early Stages of EAE, and Elevated in Spinal White Matter by Treatment With Dexamethasone en
dc.type Article
dc.contributor.organization Division of Pharmacology and Pharmacotherapy
dc.contributor.organization Regenerative Neuroscience
dc.contributor.organization Divisions of Faculty of Pharmacy
dc.contributor.organization Drug Research Program
dc.description.reviewstatus Peer reviewed
dc.relation.doi https://doi.org/10.3389/fncel.2021.640084
dc.relation.issn 1662-5102
dc.rights.accesslevel openAccess
dc.type.version publishedVersion

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