Staff View
The role of MAPKs in CNS demyelination

Descriptive

TitleInfo
Title
The role of MAPKs in CNS demyelination
Name (type = personal)
NamePart (type = family)
Gokina
NamePart (type = given)
Pradeepa
NamePart (type = date)
1981-
DisplayForm
Pradeepa Gokina
Role
RoleTerm (authority = RULIB)
author
Name (type = personal)
NamePart (type = family)
Kim
NamePart (type = given)
Haesun
DisplayForm
Haesun Kim
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
chair
Name (type = personal)
NamePart (type = family)
Friedman
NamePart (type = given)
Wilma
DisplayForm
Wilma Friedman
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Jonakait
NamePart (type = given)
Mill
DisplayForm
Mill Jonakait
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
internal member
Name (type = personal)
NamePart (type = family)
Wood
NamePart (type = given)
Teresa
DisplayForm
Teresa Wood
Affiliation
Advisory Committee
Role
RoleTerm (authority = RULIB)
outside member
Name (type = corporate)
NamePart
Rutgers University
Role
RoleTerm (authority = RULIB)
degree grantor
Name (type = corporate)
NamePart
Graduate School - Newark
Role
RoleTerm (authority = RULIB)
school
TypeOfResource
Text
Genre (authority = marcgt)
theses
OriginInfo
DateCreated (qualifier = exact)
2013
DateOther (qualifier = exact); (type = degree)
2013-10
Place
PlaceTerm (type = code)
xx
Language
LanguageTerm (authority = ISO639-2b); (type = code)
eng
Abstract (type = abstract)
MAPKs are protein kinases that play crucial roles in regulating cell proliferation, survival and differentiation. In the central nervous system (CNS), p38 MAPK and Erk1/2 play an essential role during development of the oligodendrocyte lineage and are necessary for myelination. However, the effects on mature myelin, particularly under pathological conditions remain unclear. In various neurodegenerative diseases, mature myelin deteriorates, leading to myelin loss and neuronal dysfunction. Several growth factors and cytokines are found to be increased in the demyelinated lesions suggesting that the extracellular stimuli may contribute to the myelin pathology and the subsequent changes in oligodendrocyte phenotypes. In this study, we investigated the effects of growth factor signaling on mature oligodendrocytes and the myelin. Specifically, we investigated the role of Erk1/2 and p38 MAPK activation in triggering oligodendrocyte demyelination. Using an in vitro model for CNS demyelination, we show that growth factors that are found upregulated in CNS lesions, such as FGF-2 promotes myelin breakdown through activation of the Erk1/2 and p38 MAPK pathways. We also show that ectopic activation of either Erk1/2 or p38 MAPK is sufficient to induce demyelination. Our study also indicates that growth factor or MAPK-induced demyelination was not associated with cell death, indicating the possibility of oligodendrocyte de-differentiation. To further investigate this, in chapter three we characterized the phenotype of mature oligodendrocytes following MAPK activation. Ectopic activation of Erk1/2 in mature oligodendrocytes resulted in the down-regulation of myelin proteins and a drastic change in cell morphology. A similar phenotypic change was also observed upon ectopic activation of p38 MAPK. Interestingly, after inducing the phenotypic changes, Erk1/2 activation but not p38 MAPK was sufficient to direct non-proliferating mature oligodendrocytes to re-enter the cell cycle. This result suggests that mature oligodendrocytes may have the ability to regenerate and remyelinate following the myelin loss. These studies also demonstrate that MAPKs are crucial in regulating this process. In chapter four, we investigated whether Erk1/2 mediates oligodendrocyte demyelination induced under pathological conditions. To this end, we used an in vitro model for white matter injury in which diffused axon injury is mimicked by mechanical stretching of the myelinated axons in culture. Our data shows that axonal stretch injury induces oligodendrocyte demyelination independent of axon degeneration and inhibition of Erk1/2 activation has a protective effect on the myelin. Altogether, these results suggest that MAPKs play an essential role in triggering oligodendrocyte demyelination and promoting phenotypic changes that may contribute to the subsequent regenerative process of remyelination.
Subject (authority = RUETD)
Topic
Biology
RelatedItem (type = host)
TitleInfo
Title
Rutgers University Electronic Theses and Dissertations
Identifier (type = RULIB)
ETD
Identifier
ETD_5017
PhysicalDescription
Form (authority = gmd)
electronic resource
InternetMediaType
application/pdf
InternetMediaType
text/xml
Extent
viii, 158 p. : ill.
Note (type = degree)
Ph.D.
Note (type = bibliography)
Includes bibliographical references
Note (type = vita)
Includes vita
Note (type = statement of responsibility)
by Pradeepa Gokina
Subject (authority = ETD-LCSH)
Topic
Mitogen-activated protein kinases
Subject (authority = ETD-LCSH)
Topic
Demyelination
Subject (authority = ETD-LCSH)
Topic
Oligodendroglia
RelatedItem (type = host)
TitleInfo
Title
Graduate School - Newark Electronic Theses and Dissertations
Identifier (type = local)
rucore10002600001
Location
PhysicalLocation (authority = marcorg); (displayLabel = Rutgers, The State University of New Jersey)
NjNbRU
Identifier (type = doi)
doi:10.7282/T3V122S3
Genre (authority = ExL-Esploro)
ETD doctoral
Back to the top

Rights

RightsDeclaration (ID = rulibRdec0006)
The author owns the copyright to this work.
RightsHolder (type = personal)
Name
FamilyName
Gokina
GivenName
Pradeepa
Role
Copyright Holder
RightsEvent
Type
Permission or license
DateTime (encoding = w3cdtf); (qualifier = exact); (point = start)
2013-09-22 23:12:51
AssociatedEntity
Name
Pradeepa Gokina
Role
Copyright holder
Affiliation
Rutgers University. Graduate School - Newark
AssociatedObject
Type
License
Name
Author Agreement License
Detail
I hereby grant to the Rutgers University Libraries and to my school the non-exclusive right to archive, reproduce and distribute my thesis or dissertation, in whole or in part, and/or my abstract, in whole or in part, in and from an electronic format, subject to the release date subsequently stipulated in this submittal form and approved by my school. I represent and stipulate that the thesis or dissertation and its abstract are my original work, that they do not infringe or violate any rights of others, and that I make these grants as the sole owner of the rights to my thesis or dissertation and its abstract. I represent that I have obtained written permissions, when necessary, from the owner(s) of each third party copyrighted matter to be included in my thesis or dissertation and will supply copies of such upon request by my school. I acknowledge that RU ETD and my school will not distribute my thesis or dissertation or its abstract if, in their reasonable judgment, they believe all such rights have not been secured. I acknowledge that I retain ownership rights to the copyright of my work. I also retain the right to use all or part of this thesis or dissertation in future works, such as articles or books.
Copyright
Status
Copyright protected
Availability
Status
Open
Reason
Permission or license
Back to the top

Technical

RULTechMD (ID = TECHNICAL1)
ContentModel
ETD
OperatingSystem (VERSION = 5.1)
windows xp
Back to the top
Version 8.4.8
Rutgers University Libraries - Copyright ©2022